tbuckley/cabot-search huggingface dataset:
Cisplatin (C) and gemcitabine (G) chemotherapy with concurrent irradiation (XRT), for the conservative treatment of invasive transitional bladder cancer (ITBC) patients: Clinical outcome and long-term follow-up in a monoinstitutional experience
Authors: O. Caffo, G. Fellin, U. Graffer, S. Mussari, A. Caldara, V. Murgia, F. Valduga, L. Tomio, E. Galligioni
Journal: Journal of Clinical Oncology (2009)

e16081 Background: C and G have synergistic activity when used in combination and are both potent radiosensitizers. In a dose finding trial, conducted in our hospital on ITBC patients using C and G with concurrent XRT, after maximum transurethral resection (TUR), the maximum tolerated dose of G was 400 mg/sqm (IJROBP 2003). On this basis, we have designed a phase II trial, which was prematurely closed, due to low accrual. We are presenting the long-term clinical outcome of the 16 patients involved in the dose-finding trial, together with that of the 9 pts enrolled in the phase II study. Methods: From June 1999 to December 2004, we have treated in our institution a consecutive series of 25 T2–4 N0 ITBC pts (median age 67 yrs, range 51–80). After macroscopically radical TUR, all pts received XRT (54 Gy in 30 fractions over 6 weeks) and concurrent C (100 mg/sqm, days 1, 22). In dose finding study G was given weekly from 200 to 500 mg/sqm: since unacceptable toxicity was observed in 2 cases (one death for toxicity) at the higher dose level, the recommended G dose for phase II trial was 400 mg/sqm on day 1,8 q 21 for 2 courses together with C and XRT. A cystoscopic re-evaluation was scheduled 6–8 weeks after treatment. Results: Except the pt died during treatment for toxicity, all the remaining 24 pts were microscopically disease free at cystoscopic re-evaluation. Seven local and 2 distant relapses have been observed so far, at a median follow-up of 66 mos. Presently, 16 pts (67%) is alive and disease-free, with 1 patient died for lung cancer. All pts alive have retained their bladder, with a normal organ function, in absence of any relevant long-term toxicity. The median survival has not been reached yet, while the OS at 7 years is 66%. The 5-year DFS, local DFS and survival without cystectomy, were 62%, 70%, and 95%, respectively. Conclusions: In our experience G + C with concurrent XRT in ITBC pts, appears encouraging, even at a long-term follow-up. Considering the 100% of complete response observed, this combination could be of interest to explore a possible enhancement of the disease control of C plus XRT, that is today the treatment of choice in the conservative therapy of ITBC. No significant financial relationships to disclose.
Phase II trial of sunitinib malate in patients with temozolomide refractory recurrent high-grade glioma
Authors: B. Neyns, C. Chaskis, M. Dujardin, H. Everaert, J. Sadones, N. N. Nupponen, A. Michotte
Journal: Journal of Clinical Oncology (2009)

2038 Background: High-grade gliomas (HGG) are characterized by neo-angiogenesis. Sunitinib is a small molecule tyrosine kinase inhibitor that inhibits multiple receptors (including VEGFR, PDGFR, and c-Kit). We investigated sunitinib for the treatment of patients (pts) with temozolomide (TMZ) refractory recurrent HGG. Methods: Pts were recruited according to a 2-stage phase II design and received a daily dose of 37.5 mg sunitinib. T1 ± Gd and T2 weighted MRI images were obtained after 4 and 8 weeks of sunitinib and q8 weeks thereafter. We assessed the antiangiogenic effect by calculating the cerebral blood volume (CBV) and cerebral blood flow (CBF) from dynamic susceptibility (DSC) based perfusion MRI and determined the lesion-to-normal-white matter CBV (CBV LTN ) and CBF (CBF LTN ) ratios. Uptake of fluorinated fenyl-methyl-alanine within the CNS was assessed by PET at baseline and reassessed in responding pts. Results: 21 pts were enrolled (median age 43 [range 34–71]; M/F 15/6; KPS 90–80: 11 pts, KPS 70–60: 10 pts). All pts had PD following surgery, RT and TMZ. A total of 142 treatment weeks (range 2–84) were evaluated; 81% of the administrations were at the 37,5 mg-, 19% at the 25 mg dose level. Most frequent AEs were: skin toxicity (gr2, n = 1; gr 3, n = 1), fatigue (gr 2, n = 4), hypertension (gr 2, n = 3), diarrhea (gr 2, n = 2), mucositis (gr 3; n = 1), afebrile- (gr 2, n = 3) and febrile neutropenia (gr 3, n = 1; gr 4, n = 1), thrombocytopenia (gr 2, n = 4; gr 3, n = 1; gr 4, n = 1), and lymphocytopenia (gr 2, n = 2; gr 3, n = 4). Decrease in CBV LTN and CBF LTN was observed in 6/14 evaluable pts after 4 weeks of sunitinib, 5/19 evaluable pts had SD on T1±Gd after 8 weeks; one pt experienced a marked clinical improvement with a reduction in the tumor metabolism on PET. After a median follow-up of 11 months, median TTP and -OS are1,6 and 3,8 months respectively. Three pts with a secondary glioblastoma (age &lt;40 year) had an objective PR when administered CCNU at PD under sunitinib (with a TTP of 2, 8 and +9 mths respectively). Characterization of the VEGFR, PDGFR, and Kit gene copy numbers and protein expression in the tumors is ongoing. Conclusions: Sunitinib at a continuous daily dose of 37.5 mg has a transient antiangiogenic effect in pts with recurrent HGG but is of insufficient clinical benefit to warrant further investigation as a single agent. [Table: see text]
Switching from the pocket-creation method to double clip and rubber-band traction in colonic endoscopic submucosal dissection
Authors: Yasutoshi Shiratori, Takaaki Yoshimoto, Takashi Ikeya
Journal: Endoscopy (2020)

Endoscopic submucosal dissection (ESD) has become the standard treatment for large superficial colorectal neoplasms. The pocket-creation method developed in Japan is safe and has a high en bloc resection rate [1]. However, the method cannot be completed if the fibrosis is severe or the approach to the lesion is unstable [2]. These technical difficulties necessitate a switch in strategy. We demonstrate the effective treatment of colonic neoplasms by switching the ESD strategy from the pocket-creation method to the double clip and rubber-band traction method ([Fig. 1 a – d]), now rapidly accepted in the Western countries [3] [4] ([Video 1]).
Abstract 16401: Importance of the Medical Interview: Are Prolonged Chest Symptoms the Index for Vasospastic Angina With a Higher Activity?
Authors: Hiroki Teragawa, Chikage Oshita, Yuichi Orita, Yasuki Kihara
Journal: Circulation (2019)

Introduction: We sometimes observe prolonged chest symptoms in patients with vasospastic angina (VSA). However, it has not, as of yet, been fully clarified which clinical characteristics do patient...
The myth of generalisability in clinical research and machine learning in health care
Authors: Joseph Futoma, Morgan Simons, Trishan Panch, Finale Doshi-Velez, Leo Anthony Celi
Journal: The Lancet Digital Health (2020)

An emphasis on overly broad notions of generalisability as it pertains to applications of machine learning in health care can overlook situations in which machine learning might provide clinical utility. We believe that this narrow focus on generalisability should be replaced with wider considerations for the ultimate goal of building machine learning systems that are useful at the bedside.
Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets
Authors: Claire S. Whyte, Gael B. Morrow, Nagyung Baik, Nuala A. Booth, Mohammed M. Jalal, Robert J. Parmer, Lindsey A. Miles, Nicola J. Mutch
Journal: Blood (2020)
Proposal for returning to routine endoscopy during the COVID-19 pandemic: what is really feasible?
Authors: Gianpiero Manes, Cristina Bezzio, Simone Saibeni
Journal: Endoscopy (2020)

Letter to: ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemicEndoscopy 2020; 52(06): 483-490DOI: 10.1055/a-1155-6229
High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment
Authors: Lissete Sánchez-Magraner, James Miles, Claire L. Baker, Christopher J. Applebee, Dae-Jin Lee, Somaia Elsheikh, Shaimaa Lashin, Katriona Withers, Andrew G. Watts, Richard Parry, Christine Edmead, Jose Ignacio Lopez, Raj Mehta, Antoine Italiano, Stephen G. Ward, Peter J. Parker, Banafshé Larijani
Journal: Cancer Research (2020)

Many cancers are termed immunoevasive due to expression of immunomodulatory ligands. Programmed death ligand-1 (PD-L1) and cluster of differentiation 80/86 (CD80/86) interact with their receptors, programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively, on tumor-infiltrating leukocytes eliciting immunosuppression. Immunotherapies aimed at blocking these interactions are revolutionizing cancer treatments, albeit in an inadequately described patient subset. To address the issue of patient stratification for immune checkpoint intervention, we quantitatively imaged PD-1/PD-L1 interactions in tumor samples from patients, employing an assay that readily detects these intercellular protein-protein interactions in the less than or equal to 10 nm range. These analyses across multiple patient cohorts demonstrated the intercancer, interpatient, and intratumoral heterogeneity of interacting immune checkpoints. The PD-1/PD-L1 interaction was not correlated with clinical PD-L1 expression scores in malignant melanoma. Crucially, among anti-PD-1-treated patients with metastatic non-small cell lung cancer, those with lower PD-1/PD-L1 interaction had significantly worsened survival. It is surmised that within tumors selecting for an elevated level of PD-1/PD-L1 interaction, there is a greater dependence on this pathway for immune evasion and hence, they exhibit more impressive patient response to intervention. SIGNIFICANCE: Quantitation of immune checkpoint interaction by direct imaging demonstrates that immunotherapy-treated patients with metastatic NSCLC with a low extent of PD-1/PD-L1 interaction show significantly worse outcome.
Activity of bortezomib (B) in plasma cell dyscrasia (PCD) with POEMS-like syndrome
Authors: P. A. Haddad
Journal: Journal of Clinical Oncology (2009)

e19564 Background: POEMS (polyneuropathy, organomegaly, endocrinopathy, m-protein, and skin changes) syndrome is a rare multi-system disorder associated with PCD. Although several reports revealed significant clinical benefit of IMIDs in POEMS syndrome cases that are not transplant candidates, no such published reports of B in this disease were found. Methods: We report the first case of PCD with POEMS like syndrome in addition to pulmonary hypertension, secondary right heart failure, and membranoproliferative glomerulonephritis that was successfully treated with single agent B. After presenting with the aforementioned signs and symptoms, a 64 year old white man, was diagnosed with PCD (bone marrow plasma cells 15%, IgG-λ, mild-moderate anemia, normal PET/CT, normal Cr and Ca) with ISS stage III. Due to being high risk for thromboembolic events, he was started on single agent B at 1.3mg/m2 days 1,4,8,11 Q21 days (cycles 1–4) which was reduced to 1.0mg/m2 days 1,4,8,11 Q21 days (cycles 5–6) due to grade 1 thrombocytopenia and neuropathy. This was followed by 3 maintenance cycles of 4 out of 5 weekly 1.0mg/m2. Results: Patient's breathing was subjectively better after cycle#1 despite experiencing side-effects from his pulmonary hypertension medications which had to be held and subsequently improved back to his baseline by cycle#4. By cycle#2, he was found to be in nCR with complete normalization of his bone marrow and serum electrophoresis by the end of therapy. He has been in nCR for almost 12 months so far. By cycle#3 his Raynaud's syndrome was significantly better with less dysesthesia which completely resolved by cycle#6. Conclusions: This case demonstrates for the first time the significant activity of B as a single agent in PCD with POEMS like syndrome. Further evaluation of the role of B as a first line agent in this disease, whether as single agent or in combination, is warranted. [Table: see text]
Does delay of adjuvant chemotherapy affect the clinical outcome in patients with colon cancer?
Authors: U. D. Bayraktar, S. Bayraktar, S. Herna, N. Ku, C. Jones, J. Merchan, L. R. Sands, F. Marchetti, A. Montero, C. M. Rocha-Lima
Journal: Journal of Clinical Oncology (2009)

4046 Background: Adjuvant chemotherapy (AC) in patients with stage III colon adenocarcinoma prevents recurrences and improves survival. Although most trials mandate initiation of AC within 8 weeks of resection, the impact of timing of AC is still not clear with few studies reporting conflicting results. We hypothesized that AC commenced within 60 days of resection would increase survival in patients with stage II and III colon cancer. Methods: Patients with newly diagnosed stage II or III colon adenocarcinoma who received fluoropyrimidine based AC in two centers (a private cancer center and a large community hospital) between 2000 and 2007 were included into analysis. Time to adjuvant chemotherapy (TTC), overall survival (OS), and relapse-free survival (RFS) were calculated from the surgery date. Patients were dichotomized into early- (group 1) and late-treatment (group 2) groups using the TTC of 60 days. The demographic, clinical, and laboratory characteristics of patients in two groups were compared using chi-square and t-test. Kaplan-Meier survival curves were constructed employing univariate log-rank test to assess the effects of demographic and clinical characteristics on OS. Then the impact of TTC on OS and RFS was analyzed using a Cox proportional hazard model incorporating the significant factors found in the univariate analysis. Results: 190 patients were eligible for the study (median age: 57 yrs [range 14–84]). 116 patients (61%) were female and 35 patients (18%) had stage II disease. Median TTC was 49 days (range 24–196) and median follow-up was 143 weeks (range 9–451). 134 patients (70%) received AC within 60 days of surgery (group 1) and 56 (30%) received after (group 2). The only difference between the two groups was the higher N stage in group 1. The treating hospital and the N stage were found to be the factors affecting the OS in univariate analysis. Five-year OS for group I was 75.2% as compared to 61.3% for group II (HR 2.11, CI: 1.00–4.45, p=0.049). Five-year RFS for group I was 65.7% as compared to 59.0% for group II (HR: 1.19, CI: 0.65–2.20, p=0.570). Conclusions: Delay of AC more than 60 days after resection is associated with inferior survival in stage II/III colon cancer. No significant financial relationships to disclose.
Use of age and BMD to predict fracture risk in men on androgen deprivation therapy
Authors: D. Lin, M. R. Smith, R. A. Morton, M. S. Steiner
Journal: Journal of Clinical Oncology (2009)

9517 Background: Androgen deprivation therapy (ADT) decreases bone mineral density by reducing estrogens to castrate levels and, as a result, increases fracture risk. We recently completed a two-year trial in 1382 men in which we examined the ability of toremifene to reduce fracture risk in men on ADT. Herein we describe analyses of the placebo group to assess the baseline characteristics associated with new fractures. Methods: We conducted a randomized double blind placebo controlled trial in 1382 men with histologically confirmed prostate cancer on ADT. Entry criteria included age ≥ 50 years, continous ADT for 6 months or longer or intermittent ADT for 12 months or longer. Subjects on intermittent ADT at enrollment had to remain on continuous ADT for their duration on study. Subjects were randomized to receive either 80mg toremifene citrate daily or matching placebo. The primary end point was the incidence of new morphometric vertebral fractures. Secondary endpoints included bone mineral density, clinical fragility fractures, bone turnover markers, lipid profile, hot flashes, and gynecomastia. Results: The modified intent to treat (MITT) population included subjects who took study medication and had an on-study radiograph. There were 467 subjects in the placebo MITT population. To identify factors associated with fracture risk in men on ADT we compared placebo subjects who suffered a fracture or during the first year on study suffered 7% or greater bone loss with those placebo subjects who did not. Baseline characteristics included: BMD (spine, hip, femoral neck), Age, history of fracture, ADT duration, bone turnover markers, and race. Logistic regression models of the probability of fracture/bone loss as a function of country showed that each of BMD at all sites, age, race, CTX, and history of previous fracture independently predicted fracture/7% bone loss. When all characteristics were analyzed in a multivariable model lower spine BMD (p=0.006) and older age (p=0.018) were significantly associated with incident fractures. Conclusions: In prostate cancer patients on ADT older age and lower baseline spine BMD were associated with a greater risk of fracture in untreated patients. [Table: see text]
Effects of vascular endothelial growth factor (VEGF) signaling inhibition on human erythropoiesis
Authors: M. L. Maitland, K. E. Kasza, K. L. Snider, L. Sit, E. E. Cohen, T. Y. Seiwert, T. Karrison, M. J. Ratain, E. E. Vokes
Journal: Journal of Clinical Oncology (2009)

3575 Background: In rodents, inhibition of VEGF signaling increases production of red blood cells. Major clinical trials of VEGF signaling inhibitors have not reported on these effects in human patients (pts). Methods: To determine whether disruption of VEGF signaling in humans is associated with increased erythropoiesis, we analyzed red blood cell (RBC) and hemoglobin (Hgb) measurements in pts at a single institution enrolled in a phase II trial of axitinib in advanced thyroid cancers (16 pts), a study of sorafenib in advanced solid tumors (57 pts), and a randomized phase II trial of concomitant fluorouracil, hydroxyurea, and radiation with (14 pts) or without bevacizumab (8 pts) for locally advanced cancers of the head and neck. In the axitinib and sorafenib trials, no pt received red cell transfusions (Tf) or erythropoiesis stimulating agents (ESAs). Three pts in the chemoradiotherapy study received Tf or ESAs and were excluded from further analysis. Erythropoietin (EPO) plasma concentrations were measured only on pts in the sorafenib study at baseline, and days 8 and 35. Mixed models with random intercept were used to determine the effect of VEGF signaling inhibitors on RBC and Hgb. Repeated measures analysis of variance was used to examine whether EPO levels changed over time. Results: Over the first 84 day interval of treatment RBC increased for each day on axitinib (4 K/mcl [95% CI 2, 7], p &lt; 0.001) or sorafenib (3K/mcl [2, 4], p &lt; 0.001). Similar results were detected for Hgb. For the first 68 day interval of chemoradiotherapy alone, the RBC declined over time (-13K/mcl/day [-16, -10]) but less so (-7K/mcl [-10, -5]) with added bevacizumab (interaction p = 0.003). EPO levels changed with sorafenib exposure, most notably, increasing by 38% between days 8 and 35 (p &lt; 0.001 by Wilcoxon signed rank test). Conclusions: VEGF signaling inhibition is associated with increased RBC and EPO production. This effect might contribute to positive and negative clinical consequences of exposure to VEGF signaling inhibitors. [Table: see text]
Risk of amputation with canagliflozin across categories of age and cardiovascular risk in three US nationwide databases: cohort study
Authors: Michael Fralick, Seoyoung C Kim, Sebastian Schneeweiss, Brendan M Everett, Robert J Glynn, Elisabetta Patorno
Journal: BMJ (2020)

Abstract Objective To estimate the rate of lower limb amputation among adults newly prescribed canagliflozin according to age and cardiovascular disease. Design Population based, new user, cohort study. Data sources Two commercial and Medicare claims databases, 2013-17. Participants Patients newly prescribed canagliflozin were propensity score matched 1:1 with patients newly prescribed a glucagon-like peptide-1 (GLP-1) receptor agonist. Hazard ratios and rate differences per 1000 person years were computed for the rate of lower limb amputation in the following four groups: group 1, patients aged less than 65 years without baseline cardiovascular disease; group 2, patients aged less than 65 with baseline cardiovascular disease; group 3, patients aged 65 or older without baseline cardiovascular disease; group 4, patients aged 65 or older with baseline cardiovascular disease. Within each group, pooled hazard ratio and rate difference per 1000 person years were calculated by meta-analysis. Intervention Canagliflozin versus a GLP-1 agonist. Main outcome measures Lower limb amputation requiring surgery. Results Across the three databases, 310 840 propensity score matched adults who started canagliflozin or a GLP-1 agonist were identified. The hazard ratio and rate difference per 1000 person years for amputation in adults receiving canagliflozin compared with a GLP-1 agonist for each group was: group 1, hazard ratio 1.09 (95% confidence interval 0.83 to 1.43), rate difference 0.12 (−0.31 to 0.55); group 2, hazard ratio 1.18 (0.86 to 1.62), rate difference 1.06 (−1.77 to 3.89); group 3, hazard ratio 1.30 (0.52 to 3.26), rate difference 0.47 (−0.73 to 1.67); and group 4, hazard ratio 1.73 (1.30 to 2.29), rate difference 3.66 (1.74 to 5.59). Conclusions The increase in rate of amputation with canagliflozin was small and most apparent on an absolute scale for adults aged 65 or older with baseline cardiovascular disease, resulting in a number needed to treat for an additional harmful outcome of 556 patients at six months (that is, 18 more amputations per 10 000 people who received canagliflozin). These results help to contextualize the risk of amputation with canagliflozin in routine care.
Utility and safety of bronchoscopy during the SARS-CoV-2 outbreak in Italy: a retrospective, multicentre study
Authors: Michele Mondoni, Giuseppe Francesco Sferrazza Papa, Rocco Rinaldo, Paola Faverio, Almerico Marruchella, Francesca D'Arcangelo, Alberto Pesci, Simone Pasini, Sonia Henchi, Giuseppe Cipolla, Francesco Tarantini, Lisa Giuliani, Fabiano Di Marco, Laura Saracino, Stefano Tomaselli, Angelo Corsico, Stefano Gasparini, Martina Bonifazi, Lina Zuccatosta, Laura Saderi, Giulia Pellegrino, Matteo Davì, Paolo Carlucci, Stefano Centanni, Giovanni Sotgiu
Journal: European Respiratory Journal (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the related disease (coronavirus disease 2019; COVID-19) has been notified throughout Italy since February 2020. Intensive care unit (ICU) admission rate increased following the high incidence of pneumonia-related respiratory failure [1]. Utility and safety of bronchoscopy during the SARS-CoV-2 outbreak <https://bit.ly/3ish52k> The authors wish to acknowledge Beatrice Vigo and Simona Gentile (Respiratory Unit, ASST Santi Paolo e Carlo, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy); Filippo Montanelli, Stefano Zucchetti, Giulia Pittalis, Laura Garzillo, Donatella Palmadessa, Luca Geroli and Giuseppe Paciocco (School of Medicine and Surgery, University of Milano Bicocca, Respiratory Unit, San Gerardo Hospital, ASST Monza, Monza, Italy); Vanina Rognoni (Microbiology Unit, ASST Lodi, Lodi, Italy); Daniela Zanoncelli, Isa Fenati, Teresa Goldaniga, Veena Arkasvipate and Saverio Bove (ASST Lodi, UOC Pneumologia, Lodi); and Giuseppe Ciaravino (Respiratory Unit, Papa Giovanni XXIII Hospital, Bergamo, Italy) for their valuable contribution to the research project.