tbuckley/cabot-search huggingface dataset:
Effects of antibiotic use during immunotherapy in metastatic non-small cell lung cancer
Authors: G. Galli, M. Poggi, G. Fucà, M. Imbimbo, C. Proto, D. Signorelli, M. Vitali, N. Zilembo, M. Ganzinelli, F. de Braud, M.C. Garassino, G. Lo Russo
Journal: Annals of Oncology (2018)

Background: Immunotherapy (IO) has improved the outcome of metastatic non-small cell lung cancer (mNSCLC), but only a minority of patients (pts) derives a benefit from treatment (tx). Recent evidences supported a role of gut flora in influencing systemic response against tumors. The use of antibiotics (Abs) may impair the balance of microbiota and negatively affect the efficacy of IO. We aimed at analyzing this topic in a cohort of mNSCLC pts. Methods: Data about all consecutive mNSCLC pts treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, from 04/2013 to 01/2018 were retrospectively collected. We considered relevant for the analysis the use of Abs between 1 month (mo) before and 3 mos after the beginning of IO. We also evaluated the variable "Ab exposure" (AE), defined as the % "days of ab tx/days of IO". Survival was estimated with Kaplan-Meier method; curves were compared with log-rank test. Cox proportional model was used for multivariate analyses. Results: We identified 157 cases. Most pts had a performance status (PS) ECOG ≥1 (52.2%) and ≥2 sites of metastatic disease (86.0%). IO was either an anti-PD1 (62.4%), an anti-PDL1 (32.5%), or a combination anti-PDL1/CTLA4 (5.1%); it was prescribed in first line in 25 pts, in second line in 66 pts, in a more advanced lines in 66 pts. Abs were administered to 27 pts, mostly for pneumonia. The most common were levofloxacin (55.6%), amoxi-clavulanate (25.9%) and ceftriaxone (14.8%). Progression free survival (PFS) and overall survival (OS) did not differ between Ab-treated and Ab-untreated pts (p.18; p.24, respectively). Median AE of the Ab-treated pts was 4.3% (range 0.6%-42.9%). Both PFS and OS were significantly lower in pts with a higher AE than the median one (2.2 vs 7.7 mos, p<.0001; 4.9 vs 16.3 mos, p.0004, respectively). At multivariate analysis with the other significant variables (PS and IO line), the impact of AE on PFS and OS retained significance (p.0003; p.0002, respectively). Conclusions: These results suggest that the length of Ab tx, rather than their simple use in a defined time frame, may impair the efficacy of IO. Further research is needed to support this evidence. However, it may be advisable to carefully evaluate the prescription of long Ab cycles to mNSCLC pts receiving IO. Legal entity responsible for the study: Istituto Nazionale dei Tumori. Funding: Has not received any funding. Disclosure: M. Imbimbo: Honoraria: BMS. C. Proto: Honoraria: BMS, MSD, Eli Lilly. D. Signorelli: Honoraria: AstraZeneca, Boehringer Ingelheim, BMS. M.C. Garassino: Honoraria: Roche, AstraZeneca, Boehringer Ingelheim. G. Lo Russo: Honoraria: Eli Lilly, BMS, AstraZeneca. All other authors have declared no conflicts of interest.
Global phase III trial of comparing mXELIRI+BV vs FOLFIRI+Bmab for 2nd line mCRC (AXEPT) Japanese population analysis
Authors: Takeshi Kato, Yoshinori Kagawa, Mitsuyoshi Ota, Akitaka Makiyama, Tadamichi Denda, Chu Matsuda, Yasuhide Yamada, Satoru Iwasa, Tae Won Kim, Rui-hua Xu, Young Suk Park, Satoshi Morita, Junichi Sakamoto, Kei Muro
Journal: Annals of Oncology (2018)
Unexpected Corpus Callosum Involvement of Diffuse Large B-Cell Lymphoma on FDG PET/CT
Authors: Ying Kan, Yu Wang, Wei Wang, Jie Liu, Jigang Yang
Journal: Clinical Nuclear Medicine (2018)

Diffuse large B-cell lymphoma (DLBCL) was the most frequent subtype of lymphoid malignancy. Corpus callosum involvement of DLBCL was rarely reported. We present a case of DLBCL involving not only lymph nodes and bowels but also corpus callosum, detected by FDG PET/CT in a patient without neurological symptoms. After 4 cycles of systemic and intrathecal chemotherapy, all previously visualized abnormal activity disappeared on the follow-up FDG PET/CT.
P3.09-27 Histopathologic Parameters Define Features of Treatment Response to Neoadjuvant Chemotherapy in Non-Small Cell Lung Cancer
Authors: A. Weissferdt, T. Cascone, A. Pataer, N. Kalhor, C. Moran, M.B. Antonoff, G. Walsh, C. Bernatchez, D. Gibbons, I. Wistuba, J. Roth, J. Zhang, E. Roarty, L.C.A.D.L. Landry, A. Vaporciyan, J. Heymach, S. Swisher, B. Sepesi
Journal: Journal of Thoracic Oncology (2018)
Pembrolizumab for recurrent head and neck squamous cell carcinoma (HNSCC): Post hoc analyses of treatment options from the phase III KEYNOTE-040 trial
Authors: C. Le Tourneau, E.E.W. Cohen, K.J. Harrington, J. Dinis, L. Licitra, M.-J. Ahn, A. Soria, J.-P. Machiels, N. Mach, R. Mehra, B. Burtness, P. Zhang, J. Cheng, R. Swaby, D. Soulières
Journal: Annals of Oncology (2018)
Metastatic clear cell renal cell carcinoma patients with ECOG performance status 2 treated with pazopanib: The Pazo2 trial of efficacy and safety
Authors: E. Porfiri, S. Pirrie, A.-M. Hodgkins, D. Farrugia, K. Fife, C. McDonald-Smith, N.S. Vasudev, G. Nixon, N.D. James, C. Stubbs
Journal: Annals of Oncology (2018)
Abstract 30: Global Electrical Heterogeneity on Electrocardiogram is Associated with Sudden Cardiac Death After Adjustment for Ejection Fraction
Authors: Larisa G Tereshchenko, Jonathan Waks, Mary Biggs, Colleen Sitlani, Muammar Kabir, Golriz Sedaghat, Jason Thomas, Charles Henrikson, Tor Biering-Sørensen, Sunil Agarwal, Nona Sotoodehnia, David Siscovick, Wendy Post, Scott Solomon, Elsayed Soliman, Alfred Buxton, Mark Josephson
Journal: Circulation (2016)

Introduction: Electrocardiographic (ECG) measures of myocardial global electrical heterogeneity (GEH) are associated with sudden cardiac death (SCD) in middle-age adults. Hypothesis: We hypothesized that time-updated ECG GEH measures are associated with SCD in elderly adults after LVEF adjustment. Methods: We analyzed data from 2 prospective cohorts: The Atherosclerosis Risk in Communities (ARIC, n=15,366; mean age 54.1±5.8 y; 44.6% male; 73.2% white) and the Cardiovascular Health Study (CHS, n=5,016; mean age 72.8±5.6 y; 43.1% male; 95.3% white). Mean spatial QRS-T angle, azimuth, elevation, and magnitude of spatial ventricular gradient (SVG), and sum absolute QRST integral (SAI QRST) were calculated from digital 12-lead ECGs and analyzed as baseline variables in ARIC and as time-updated longitudinal variables in CHS (measured yearly at 10 consecutive visits). The primary outcome was adjudicated SCD. Cox regression models were constructed: Model 1 adjusted for age, sex and race. Model 2 further adjusted for cardiovascular disease, beta-blocker use, creatinine, BMI, hypertension, diabetes, smoking, total cholesterol, HDL, triglycerides, physical activity and alcohol use. Model 3 included Model 2 variables and heart rate, QTc, LV hypertrophy and bundle branch block or intra-ventricular conduction delay. Model 4 in CHS included all Model 3 variables plus baseline LVEF and time-updated incident HF and coronary heart disease. Results: During median 13-14 y of follow-up SCD incidence was 1.51 (95%CI 1.35-1.69) per 1,000 person-yrs in ARIC, and 2.78 (95%CI 2.41-3.21) per 1,000 person-yrs in CHS. In both cohorts (Table) QRS-T angle, SVG and SAI QRST were associated with SCD. Among older adults (CHS), longitudinal SAI QRST, QRS-T angle and SVG magnitude were associated with SCD independent of LVEF. Conclusions: Baseline and longitudinal GEH ECG parameters are independently associated with SCD in middle-age and older adults, respectively. In older adults, GEH ECG parameters provide information on SCD risk beyond LVEF.
Immune stimulation and photodynamic therapy to treat a metastatic model of breast cancer
Authors: Ana P. Castano, Michael R. Hamblin
Journal: Cancer Research (2006)

4781  One in 8 women in the United States will develop breast cancer during her lifetime and 40,000 die each year. Deaths are due to tumors that have metastasized despite local control. Photodynamic therapy (PDT) is a promising cancer treatment in which a photosensitizer (PS) accumulates in tumors and is subsequently activated by visible light of an appropriate wavelength. The energy of the light is transferred to molecular oxygen to produce reactive oxygen species that produce cell death and tumor ablation. Mechanisms include cytotoxicity to tumor cells, shutting down of the tumor vasculature, and the induction of a host immune response. The precise mechanisms involved in the PDT-mediated induction of anti-tumor immunity are not yet understood. Potential contributing factors are alterations in the tumor microenvironment via stimulation of proinflammatory cytokines and direct effects of PDT on the tumor that increase immunogenicity. We have studied PDT of 4T1 variant 410.4 tumors growing in the mammary fat pad (orthotopic) in Balb/c mice and which produce metastasis. We have shown that a PDT regimen that produces vascular shutdown and tumor necrosis leads to initial tumor ablation but the tumors recur at the periphery. We studied the combination of PDT with immunostimulating therapies. Low dose cyclophosphamide (CY) is a specific mechanism to deplete the regulatory T cells (CD4+CD25+), these cells play an important role in the immunosuppression activity of tumors. In combination with PDT that pro duces release of tumor specific antigens, this immunostimulation may lead to generation of cytotoxic CD8 T-lymphocytes that recognize and destroy the tumor. The second alternative therapy is the use of a novel combination of the immunostimulant CpG oligodeoxynucleotides (CpG-ODN) and PDT. CpG-ODN is recognized by Toll-like receptor 9 and directly or indirectly triggers B cells, NK cells, monocyte-macrophages and dendritic cells to proliferate, mature and secrete cytokines, chemokines and immunoglobulins. Both these novel combinations gave significantly enhanced therapeutic benefit not seen with single treatments alone. Tumors grew more slowly and mice lived significantly longer, although cures were rare. We propose that a rational choice of immune stimulant is an ideal addition to PDT regimens.
Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party
Authors: Sujith Samarasinghe, Katherine Clesham, Simona Iacobelli, Giulia Sbianchi, Cora Knol, Rose‐Marie Hamladji, Gerard Socié, Mahmoud Aljurf, Mickey Koh, Henrik Sengeloev, Jean‐Hugues Dalle, Stephen Robinson, Maria Teresa Van Lint, Constantijn J. M. Halkes, Dietrich Beelen, Ghulam J. Mufti, John Snowden, Didier Blaise, Regis Peffault de Latour, Judith Marsh, Carlo Dufour, Antonio M Risitano
Journal: American Journal of Hematology (2018)

Abstract We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) ( n = 1283), alemtuzumab ( n = 261), or no serotherapy (NS) ( n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS ( P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG ( P = .012) and NS ( P &lt; .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P &lt; .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS ( P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.
Ketone Body Infusion Increases Circulating Erythropoietin and Bone Marrow Glucose Uptake
Authors: Katrine M. Lauritsen, Esben Søndergaard, Mads Svart, Niels Møller, Lars C. Gormsen
Journal: Diabetes Care (2018)

Sodium–glucose cotransporter 2 (SGLT2) inhibition was originally developed as a facile way of lowering blood glucose through increased renal elimination. However, clinical trials have demonstrated that SGLT2 inhibition not only improves glycemic control but also increases circulating ketone bodies and hematocrit (1,2). Recently, SGLT2 inhibitor–driven modest hyperketonemia has attracted much focus as a possible explanation of the improved cardiac outcome in patients treated with SGLT2 inhibitors (3), whereas the increased hematocrit has mostly been ascribed to hemoconcentration due to increased osmotic diuresis. In this Observation, we present data indicating that hyperketonemia directly stimulates circulating erythropoietin concentrations and is associated with increased bone marrow activity assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).

Seventeen healthy subjects undergoing either cardiac (study A) or brain (study B) PET/CT as part of protocols involving experimental hyperketonemia were investigated. Study A (4) consisted of 8 subjects (3 women) aged mean 60 (range 50–68) years with BMI mean 26 (range 22–35) kg/m2, and study B (5) of 9 subjects (4 women) aged 62 (56–69) years with BMI 24 (21–27) kg/m2. Both studies were randomized, single-blinded crossover trials in which participants were infused with either 7.5% Na-3-β-hydroxybutyrate (3-OHB) (infusion rate 0.18 g/kg/h [study A] and 0.22 g/kg/h [study B]) or saline (0.9%). In study A, bone marrow palmitate and glucose uptake …
Malaria prevention: from immunological concepts to effective vaccines and protective antibodies
Authors: Ian A. Cockburn, Robert A. Seder
Journal: Nature Immunology (2018)

Development of a malaria vaccine remains a critical priority to decrease clinical disease and mortality and facilitate eradication. Accordingly, RTS,S, a protein-subunit vaccine, has completed phase III clinical trials and confers ~30% protection against clinical infection over 4 years. Whole-attenuated-sporozoite and viral-subunit vaccines induce between 20% and 100% protection against controlled human malaria infection, but there is limited published evidence to date for durable, high-level efficacy (>50%) against natural exposure. Importantly, fundamental scientific advances related to the potency, durability, breadth and location of immune responses will be required for improving vaccine efficacy with these and other vaccine approaches. In this Review, we focus on the current understanding of immunological mechanisms of protection from animal models and human vaccine studies, and on how these data should inform the development of next-generation vaccines. Furthermore, we introduce the concept of using passive immunization with monoclonal antibodies as a new approach to prevent and eliminate malaria.
Effects of prenatal exercise on incidence of congenital anomalies and hyperthermia: a systematic review and meta-analysis
Authors: Margie H Davenport, Courtney Yoo, Michelle F Mottola, Veronica J Poitras, Alejandra Jaramillo Garcia, Casey E Gray, Nick Barrowman, Gregory A Davies, Amariah Kathol, Rachel J Skow, Victoria L Meah, Laurel Riske, Frances Sobierajski, Marina James, Taniya S Nagpal, Andree-Anne Marchand, Linda G Slater, Kristi B Adamo, Ruben Barakat, Stephanie-May Ruchat
Journal: British Journal of Sports Medicine (2018)

Objective To investigate the relationships between exercise and incidence of congenital anomalies and hyperthermia. Design Systematic review with random-effects meta-analysis . Data sources Online databases were searched from inception up to 6 January 2017. Study eligibility criteria Studies of all designs were eligible (except case studies and reviews) if they were published in English, Spanish or French, and contained information on population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone [“exercise-only”] or in combination with other intervention components [e.g., dietary; “exercise + co-intervention”]), comparator (no exercise or different frequency, intensity, duration, volume or type of exercise) and outcome (maternal temperature and fetal anomalies). Results This systematic review and meta-analysis included ‘very low’ quality evidence from 14 studies (n=78 735) reporting on prenatal exercise and the odds of congenital anomalies, and ‘very low’ to ‘low’ quality evidence from 15 studies (n=447) reporting on maternal temperature response to prenatal exercise. Prenatal exercise did not increase the odds of congenital anomalies (OR 1.23, 95% CI 0.77 to 1.95, I 2 =0%). A small but significant increase in maternal temperature was observed from pre-exercise to both during and immediately after exercise (during: 0.26°C, 95% CI 0.12 to 0.40, I 2 =70%; following: 0.24°C, 95% CI 0.17 to 0.31, I 2 =47%). Summary/Conclusions These data suggest that moderate-to-vigorous prenatal exercise does not induce hyperthermia or increase the odds of congenital anomalies. However, exercise responses were investigated in most studies after 12 weeks’ gestation when the risk of de novo congenital anomalies is negligible.
SHROOM3-FYN Interaction Regulates Nephrin Phosphorylation and Affects Albuminuria in Allografts
Authors: Chengguo Wei, Khadija Banu, Felipe Garzon, John M. Basgen, Nimrod Philippe, Zhengzi Yi, Ruijie Liu, Jui Choudhuri, Miguel Fribourg, Tong Liu, Arun Cumpelik, Jenny Wong, Mubeen Khan, Bhaskar Das, Karen Keung, Fadi Salem, Kirk N. Campbell, Lewis Kaufman, Paolo Cravedi, Weijia Zhang, Philip J. O'Connell, John Cijiang He, Barbara Murphy, Madhav C. Menon
Journal: Journal of the American Society of Nephrology (2018)

We previously showed that the presence of a CKD-associated locus in SHROOM3 in a donor kidney results in increased expression of SHROOM3 (an F-actin-binding protein important for epithelial morphogenesis, via rho-kinase [ROCK] binding); this facilitates TGF-b signaling and allograft fibrosis. However, other evidence suggests Shroom3 may have a protective role in glomerular development.We used human data, Shroom3 knockdown podocytes, and inducible shRNA-mediated knockdown mice to study the role of Shroom3 in adult glomeruli.Expression data from the Nephroseq database showed glomerular and nonglomerular SHROOM3 had opposing associations with renal function in CKD biopsy samples. In human allografts, homozygosity at rs17319721, the SHROOM3 locus linked with lower GFR, was associated with reduced albuminuria by 2 years after transplant. Although our previous data showed reduced renal fibrosis with tubular Shroom3 knockdown, this study found that glomerular but not tubular Shroom3 knockdown induced albuminuria. Electron microscopy revealed diffuse foot process effacement, and glomerular RNA-sequencing showed enrichment of tyrosine kinase signaling and podocyte actin cytoskeleton pathways in knockdown mice. Screening SHROOM3-interacting proteins identified FYN (a src-kinase) as a candidate.We confirmed the interaction of endogenous SHROOM3 with FYN in human podocytes via a critical Src homology 3-binding domain, distinct from its ROCK-binding domain. Shroom3-Fyn interaction was required in vitro and in vivo for activation of Fyn kinase and downstream nephrin phosphorylation in podocytes. SHROOM3 knockdown altered podocyte morphology, cytoskeleton, adhesion, and migration.We demonstrate a novel mechanism that may explain SHROOM3's dichotomous associations in glomerular versus nonglomerular compartments in CKD.
Single LAMS versus multigate plastic stent drainage of WON; fair comparison or apples versus oranges?
Authors: James Leonard Buxbaum
Journal: Gut (2018)

In the recent edition of Gut , Bang et al present an important randomised trial comparing lumen-apposing metal stents (LAMS) versus plastic endoprostheses for the drainage of walled-off pancreatic necrosis (WON).1 The authors demonstrate that caution needs to be exercised when using LAMS for this indication given that they may induce …
Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype?
Authors: Gabor Kovacs, Alvar Agusti, Joan Albert Barberà, Bartolome Celli, Gerard Criner, Marc Humbert, Don D. Sin, Norbert Voelkel, Horst Olschewski
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Although often clinically unrecognized, the pulmonary circulation is frequently affected in patients with chronic obstructive pulmonary disease (COPD), and the presence of pulmonary vascular disease is associated with poor prognosis and frequent exacerbations. In most cases the presenting pulmonary hypertension (PH) is relatively mild, but in a subset of COPD patients, the presence of certain clinical features supports the existence of a “pulmonary vascular phenotype”. Such a phenotype would be characterized by severe pre-capillary PH with strongly elevated pulmonary vascular resistance, moderate airflow limitation, severely decreased diffusion capacity for carbon monoxide, normo- or hypocapnia, circulatory exercise limitation and progressive right heart failure. Additional molecular and genetic features of this phenotype have been suggested. Although current PH guidelines do not suggest targeted therapy with pulmonary arterial hypertension drugs for COPD patients and prospective controlled studies are la...
Inhibitors of the protein disulfide isomerase family for the treatment of multiple myeloma
Authors: Reeder M. Robinson, Leticia Reyes, Ravyn M. Duncan, Haiyan Bian, Allen B. Reitz, Yefim Manevich, Jesse J. McClure, Matthew M. Champion, C. James Chou, Meahgen E. Sharik, Marta Chesi, P. Leif Bergsagel, Nathan G. Dolloff
Journal: Leukemia (2018)
Abstract 17868: Digoxin Eliminates the Antiarrhythmic Effect of Ranolazine in RAID Trial
Authors: Mark C Haigney, Scott McNitt, Christopher Beck, James Daubert, Samir Saba, Arthur Moss, Wojciech Zareba
Journal: Circulation (2017)

Introduction: Ranolazine (RAN) is a late-Na current blocker that is an inhibitor of the P-glycoprotein elimination pathway. The RAID trial tested whether RAN exerts an antiarrhythmic effect in high...
Abstract 14455: A New 4-Variable Formula to Differentiate Early Repolarization From Subtle Left Anterior Descending Coronary Occlusion -- Adding QRS Amplitude of V2 Improves the Model
Authors: Stephen W Smith, Amina Adil, Faraz Kazmi, Brian E Driver
Journal: Circulation (2016)

Introduction: Precordial normal variant ST elevation (STE), or “early repolarization” (ER), may be difficult to differentiate from subtle ischemic STE due to LAD occlusion. We previously derived an...
GW29-e0636 The Study of the Effects of Intracoronary Recombinant Human Prourokinase or Tirofiban on the Coronary Flow during Primary PCI for the Acute Myocardial Infartion
Authors: Zhuhua Yao, Wenting Li, Lisong Cheng, Zhihua Pang, Mingying Cao, Hongbin Cai, Zhuhua Yao
Journal: Journal of the American College of Cardiology (2018)
GW29-e1801 Vasodilation dysfunction in cardiac catheterization laboratory workers and possible preventive effect of folic acid
Authors: Xiaofan Peng, Fan Xiang, Zhenhua Xing, Cheng Wei, Jiabin Huang, Yanan Guo, Hui Yang, Zhenfei Fang, Xinqun Hu, Jianjun Tang, Qimin Liu, Zhaowei Zhu, Zehui Liu, Shenghua Zhou
Journal: Journal of the American College of Cardiology (2018)