tbuckley/cabot-search huggingface dataset:
Preoperative rehabilitation in patients with thoracic tumors and borderline abnormal spirometry results: Preliminary report.
Authors: Oliwia Anna Glogowska, Sebastian Szmit, Hanna Tchorzewska-Korba, Maciej Glogowski
Journal: Journal of Clinical Oncology (2013)

e18529 Background: The role of preoperative pulmonary rehabilitation is unclear. The aim of the study is short-term efficacy of pulmonary rehabilitation in patients with thoracic tumors and borderline abnormal spirometry results before thoracic surgery. Methods: We observed 12 patients (7 women, 5 men) in mean age of 64 (range 46-82) years. Clinical inclusion criteria were: diagnosis of thoracic tumors and reduced values of FEV1 and FVC predicting postoperative complications. Spirometry and 6MWT were chosen for evaluation of lung function and physical performance during rehabilitation. These tests were performed twice during screening phase to eliminate the factors of learning, and were repeated after first and second week of rehabilitation. Pulmonary rehabilitation included two weeks of training on the treadmill with individually selected speed, physiotherapy exercises and breathing training with using of Triflo. Results: The analyses of results of spirometry and 6MWT before and after 2 weeks of pulmonary rehabilitation indicated the significant differences in values of: 1)FEV1 (L): 1,38 ± 0,23 vs 1,61 ± 0,29 (p=0,01) 2) FEV1 (%N): 56,3 ± 13,9 vs 67,8 ± (p=0,007) 3) FVC (L): 2,24 ± 0,37 vs 2,74 ± 0,67 (p=0,03) 4) FVC (%N): 73,5 ± 15,7 vs 91,2 ± 12,7 (p=0,01) 5) 6MWT distance (m): 251 ± 79 vs 310 ± 74 (p=0,003). Although improvement after rehabilitation, 3 patients were disqualified from lobectomy due to unsatisfactory performance status. Another 3 patients experienced complications during perioperative period. Analysis of pulmonary rehabilitation efficacy showed that 6 patients with favourite outcome after thoracic surgery differed significantly in comparing to others. They achieved significantly higher difference in following parameters: 1) FEV1 (L): 0,4 vs 0,06 (p=0,02) 2) FVC (L): 0,91 vs 0,09 (p=0,02) 3) 6MWT distance (m): 93 vs 25 (p=0,016). Conclusions: A two-week pulmonary rehabilitation leads to significant improvement of lung function and physical performance in patients with thoracic tumors and borderline abnormal spirometry results. A clinically significant increase of absolute values of FEV1, FVC and 6MWT distance may indicate a favourite outcome after thoracic surgery.
CTLs/regulatory T-cells ratio as a prediction marker of chemotherapy in metastatic colorectal cancer.
Authors: Teruo Sasatomi, Takafumi Oochi, Yutaka Ogata, Yoshito Akagi, Kazuo Shirouzu
Journal: Journal of Clinical Oncology (2013)

e14684 Background: Many multiple anti cancer drugs regimens have been established for metastaticcolorectal cancer recently. We investigated cellular immunoreaction of these patients to their cancer. Methods: 32 metastatic colorectal cancer patients have been started chemotherapies. Their PBMCs were harvested and investigated their character by Fac scan with fluorescent labeled antibodies (CD3,CD8, CD4, CD25, Foxp3) at before and after chemotherapy. Results: After chemotherapy, both CTLs(CD3, CD8 positive) and regulatory T cells (CD4, CD25, Foxp3 positive) were decreased in number among all patients. On the other hand, CTL/T reg ratio were significantly increased among tumor marker decreased patients and significantly decreased among tumor marker increased or stable patients. CEA levels among 85.7% of increased CTL/T reg ratio patients became to decrease less thanhalf. CEA levels among 66.7% of decreased CTL/T reg ratio patients became to increase or to be stable, if their regimens have not been changed. The Reactive Rate of chemotherapy of CTL/T reg ratio increased patients was significantly higher than that of ratio decreased or stable patients. (P=0.021) The Disease Control Rate of chemotherapy of CTL/T reg ratio increased patients was higher than that of ratio decreased patients. Both resectability rate of liver metastatic lesion and early tumor shrinkage rate were higher at the CTL/T reg ratio increased patients group than at the other patients group. Conclusions: We found that the CTL/T reg ratios of PBMC in metastatic colorectal cancer patients were useful for prediction of the effect of chemotherapy.
Phosphatidylserine targeting antibody in combination with anti-PD-1 antibody treatment activates infiltrating T lymphocytes of the spleen and tumor microenvironment in pre-clinical models of melanoma and breast cancer.
Authors: Xianming Huang, Jian Gong, Van Nguyen, Shen Yin, Carrie Baldwin, Rolf A. Brekken, Steven King, Jeff Hutchins, Bruce Freimark
Journal: Journal of Clinical Oncology (2015)

3059 Background: Despite substantial progress, only a select subset of patients benefit from anti-PD-1/PD-L1 therapies. The underlying cause for these failures of immune checkpoint blockade therapy is the overwhelming, persistent and multifocal immune suppression within the tumor microenvironment. As phosphatidylserine (PS) becomes externalized to the outer leaflet of the cell’s plasma membrane within the tumor microenvironment, it serves as a signaling ligand for PS receptors on immunosuppressive myeloid-derived suppressor cells (MDSCs), regulatory T cells and M2 macrophages that can occupy up to 50% of the tumor mass. Bavituximab is a chimeric monoclonal antibody that targets and inhibits PS mediated immunosuppressive signaling, supporting immune activation and reducing levels of MDSCs, re-polarizing tumor-associated macrophages from M2 to M1 phenotype, promoting the maturation of dendritic cells (DCs) and inducing potent antitumor T-cell immunity. Methods: A combination of bavituximab and anti-PD-1 therapy was compared in syngeneic, pre-clinical models of melanoma and breast cancer. Results: Our results show that the combination induces a statistically significant activation of lymphocytes in the spleen and the tumor microenvironment as well as decreases MDSCs and PD-L1 expression. In the spleen, increases were noted in T-cells producing IFN-g and IL-2 and DCs in association with decreased MDSCs over single anti-PD-1 treatment alone. Similarly, in the tumor microenvironment, the combination treatment demonstrates increases in TILs producing IFN-g, TNFα, IL-2, Granzyme B, PD-1, increased Lag-3 positive CD8 cells, CD137 (41BB) positive CD4 cells as well as a decrease in MDSCs and PD-L1 expressing TILs compared to anti-PD-1 treatment alone. Conclusions: Our pre-clinical results support the use of bavituximab as an immunomodulatory treatment in PD-1 sensitive and anti-PD-1 resistant/unresponsive tumors. This effect involves enhancing the activation of CD8+ TIL correlating with increased immune stimulatory components in the spleen and the tumor microenvironment.
Pharmacokinetics of moxifloxacin and linezolid during and after pregnancy in a patient with multidrug-resistant tuberculosis
Authors: Els Van Kampenhout, Mathieu S. Bolhuis, Jan-Willem C. Alffenaar, Laurien M.A. Oswald, Huib A.M. Kerstjens, Wiel C.M. de Lange, Tjip S. van der Werf, Onno W. Akkerman
Journal: European Respiratory Journal (2017)

Worldwide, tuberculosis (TB) is among the top five causes of death for women aged 15–44 years [1]. In 2014, an estimated 480 000 of newly reported TB cases were multidrug-resistant (MDR) TB [1]. Pregnancy is a risk factor for reactivation of TB, but data about multidrug-resistant (MDR)-TB in pregnant women are lacking. There are few data about the efficacy and safety of second-line anti-TB drugs during pregnancy for both the mother and the unborn child [2]. One study from Peru showed a mortality rate of 13% in 38 patients and 13% of these 38 patients were lost to follow-up. Five of the pregnancies ended in spontaneous abortions, and one child was stillborn. Data for pregnant women did not differ from the general MDR-TB population in Peru [2]. Pharmacokinetics of moxifloxacin and linezolid during and after pregnancy in an MDR-TB patient <http://ow.ly/Ind2308nLlB>
Pilot skin microbiome study of patients with pancreatic cancer in comparison to patients with other malignancies as well as those without cancer.
Authors: Erkut Hasan Borazanci, Gayle S. Jameson, Jade Hess, Evan Gelzayd, Sasan Amini, Dana Hosseini, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2017)

TPS502 Background: The microbiome is a burgeoning field involving the study of the microbial flora in humans and its effect on health. The human microbiome is altered by several environmental factors and may play a great role in inflammation and possibly in the development in several malignancies including pancreatic cancer. The purpose of this study is to characterize the skin microbiomes on the forehead and cheek of people with pancreas cancer compared to people with other forms of cancer and people without cancer by utilizing the ProdermIQ skin profiling platform. Methods: This is a prospective, open-label, pilot study. Sampling will be done as one time collection after informed consent through a skin swab on the forehead and one on the cheek. Subjects with a diagnosis of pancreatic adenocarcinoma, subjects with a diagnosis of malignancy other than pancreatic adenocarcinoma, and subjects without a diagnosis of malignancy will be enrolled for three separate arms of the study. Each study arm is composed of 25 individuals for a total of 75. Key inclusion criteria include subjects at least 18 years of age and a histologically confirmed diagnosis of pancreatic adenocarcinoma in the pancreas arm; a histological confirmed diagnosis of a malignancy other than pancreatic cancer in the other cancer arm; and individuals without cancer. Individuals with a rash or skin disorder will be excluded from the study. Once all swabs are collected they will be batch tested through next generation sequencing to characterize the skin microbiomes. A comprehensive comparison will be constructed of the profiles of each study group.
PKC412 (midostaurin) is safe and highly effective in systemic mastocytosis: Follow up of a single-center Italian compassionate use.
Authors: Cristina Papayannidis, Simona Soverini, Caterina De Benedittis, Michela Rondoni, Mariachiara Abbenante, Chiara Sartor, Ilaria Iacobucci, Francesca Volpato, Carmen Baldazzi, Emanuela Ottaviani, Anna Ferrari, Viviana Guadagnuolo, Alberto Conficoni, Stefania Paolini, Sarah Parisi, Federica Frabetti, Silvia Piccari, Elisa Lani, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2014)

7113 Background: Treatment of SM usually focuses on symptom relief by histamine receptor antagonists and other supportive therapy. However, in aggressive and leukemic variants, cytoreductive and targeted drugs must be applied. Methods: From 2008, 22 patients (male/female=11/11) affected by SM have been referred to our Institution. Twelve (55%) was diagnosed with ASM, presenting with systemic symptoms associated with signs of organ involvement (skeletal lesions, ascites, liver function impairment or bon marrow disfunction). Therefore, due to the failure of a first line therapy (IFNalfa, Imatinib and 2CdA in 56%, 11% and 33% of the patients, respectively), a personalized use of PKC412 was asked and obtained for 9 out of 12 ASM patients. Thus, from March 2011, 9 (M/F =3/9) patients with ASM have been treated with PKC412, administered orally, at the dosage of 100 mg twice daily, continuously. The median age was 60 years (range 39-75); the median time from diagnosis was 6 months (range 2-53). Median serum tryptase level was 100 mcg/L(range 19.3-1160). C-kit mutation D816V was present in 8 out of 9 patients. Cytogenetic analysis was normal in all the patients. Results: Seven out of nine patients were evaluable for response. The median duration of therapy was 517 days (range 327-970+). According to European Criteria, a Major response was observed in one patient, and a partial response in 6 patients. Overall, the drug was well tolerated, and no serious adverse events were observed. All the patients obtained a quick improvement of clinical symptoms, in terms of weight gain, bowel function and skeletal pain. At the bone marrow evaluation, the persistence of the D816V c-kit mutation was observed, despite a significant decrease of mast cell marrow involvement. Conclusions: In a small cohort of ASM patients, the prolonged therapy with PKC412 is safe and effective, mainly on symptoms improvement and haematological profile. Nevertheless, the persistence of the D816V c-kit mutation suggests that many other oncogenic factors may be responsible for the pathogenesis of the disease.
Time to response (TTR) and early tumor shrinkage (ETS) in recurrent glioblastoma patients treated with bevacizumab: an exploratory analysis of the prospective randomized AVAREG (ML25739) phase II study.
Authors: Enrico Franceschi, Gaetano Finocchiaro, Vittorina Zagonel, Michele Reni, Alessandra Fabi, Claudia Caserta, Matteo Clavarezza, Evaristo Maiello, Giacomo Carteni, Giovanni Rosti, Raffaele Agati, Alicia Tosoni, Alexandro Paccapelo, Emanuela Proietti, Alba Ariela Brandes
Journal: Journal of Clinical Oncology (2015)

2047 Background: The treatment of recurrent glioblastoma (GBM) remains an open issue, and the role of bevacizumab (BEV) has been widely debated since a few studies compared this agent with the standard treatments. Methods: a multicenter, randomized (2:1), phase II study (EudraCT: 2011-001363-46) with BEV 10 mg/kg iv every 2 weeks or fotemustine (FTM) 75 mg/m2 iv day 1-8-15 followed, after a 35 days interval, by fotemustine 100 mg/m2 every 3 weeks, was conducted. The primary endpoint was overall survival at 6 months (OS-6). ETS was assessed with central review exploratory analysis. T1contrast enhancing area and T2/FLAIR were evaluated as predictors for OS rates with ROC analysis and the test for AUC. The best cut-off values were found with the maximization of Youden's Index. The groups obtained were analyzed with Kaplan-Meier procedure and compared with univariate and multivariate Cox proportional hazards model. Results: 91 patients with recurrent GBM were enrolled in 10 Italian centers between 11/2011 and 9/2012. The median age was 57 years (range: 28-78). Fifty-nine patients were enrolled in the BEV arm and 32 patients in the FTM arm. OS-6 was 62.1% (95%CI: 48.4-74.5) and 73.3% (95%CI: 54.1-87.7), OS-9 was 37.9% (95%CI: 25.5–51.6) and 46.7% (95%CI: 28.3–65.7) in the BEV and FTM arms, respectively. Median OS was 7.3 months (95%CI: 5.8-9.2) in the BEV arm and 8.7 months (95%CI: 6.3-15.4) in the FTM arm. The response rate was 29% (95%CI: 18-42) and 9% (95%CI: 2-25) for patients treated with BEV and FTM, respectively. TTR (p = 0.05, HR = 0.46, 95%CI:0.21-1.00) and ETS > 15% in T1 contrast enhancing area at first disease assessment (p = 0.040, HR = 0.511, 95%CI:0.269-0.971) could predict OS in patients treated with BEV but not with FTM (TTR and ETS with FTM: p = 0.19 and p = 0.4, respectively). Patients achieving an ETS ≥ 15% had significantly longer OS than those achieving an ETS < 15% (8.4 vs 5.2 months). Conclusions: BEV and FTM are both active drugs in recurrent GBM. TTR and ETS might be helpful predictors of GBM outcome in patients treated with BEV. Clinical trial information: NCT01474239.
Retrospective review of outcomes in patients (pts) with synchronous metastatic rectal cancer (mRC) receiving initial non-surgical management.
Authors: Ella Torti, James O Park, E. Gabriela Chiorean, Edward Y. Kim, Stacey Cohen, Andrew L. Coveler
Journal: Journal of Clinical Oncology (2017)

797 Background: Management of mRC trends toward initial non-surgical management of the primary tumor based on studies demonstrating low complications rates from un-resected primary colonic tumors. The fixed location of the rectum may increase local complications. This study characterizes complications of pts with synchronous mRC with an intact primary tumor. Methods: A retrospective review of records from 2001 to 2013 identified pts with mRC by ICD-9/10 codes. Pts with treatment-naïve mRC without significant local symptomatology were evaluated. Time to complications and death were calculated. Pathology, stage, baseline CEA, RAS, BRAF and initial treatment were evaluated for prognostic significance. Results: Forty-four pts were identified with mRC; eight were excluded for initial resection for a symptomatic primary. Among the 36 evaluable pts treated with initial chemotherapy, 14 (39%) developed complications related to the primary tumor, of whom 5 (14%) developed two or more complications. Six (17%) required operative intervention due to primary tumor complications (two died prior to planned procedure). Complications were: perforations/abscesses/fistulae (6), bowel obstruction (5), severe bleeding (5), urinary obstruction/infection (3) and, pain requiring palliative treatment (1). Interventions included blood transfusions (5), stents (3), radiotherapy (3), I&amp;D/drains (3) and, nephrostomy (2). Of 22 pts who did not develop any complications, 15 underwent curative resection of all sites of disease. Six remain disease free and nine relapsed, all distantly. None of the 14 who developed complications underwent curative operation. The median time to complication was 2.5 months. Median overall survival was 37 and 52 months for those with and without complications, respectively. Median time from complication to death was 21 months. Pts aged &gt; 50 vs &lt; 50 were more likely to have complications of the primary tumor (57% vs 21%). Conclusions: mRC pts with intact primary tumors may develop complications at a higher rate (39%) than those with colon cancer (11%). These findings will need to be confirmed with larger datasets and examine for specific treatment effects.
Facility-Level Variation in Hospitalization, Mortality, and Costs in the 30 Days After Percutaneous Coronary Intervention
Authors: Steven M. Bradley, Colin I. O’Donnell, Gary K. Grunwald, Chuan-Fen Liu, Paul L. Hebert, Thomas M. Maddox, Robert L. Jesse, Stephan D. Fihn, John S. Rumsfeld, P. Michael Ho
Journal: Circulation (2015)

Policies to reduce unnecessary hospitalizations after percutaneous coronary intervention (PCI) are intended to improve healthcare value by reducing costs while maintaining patient outcomes. Whether facility-level hospitalization rates after PCI are associated with cost of care is unknown.We studied 32,080 patients who received PCI at any 1 of 62 Veterans Affairs hospitals from 2008 to 2011. We identified facility outliers for 30-day risk-standardized hospitalization, mortality, and cost. Compared with the risk-standardized average, 2 hospitals (3.2%) had a lower-than-expected hospitalization rate, and 2 hospitals (3.2%) had a higher-than-expected hospitalization rate. We observed no statistically significant variation in facility-level risk-standardized mortality. The facility-level unadjusted median per patient 30-day total cost was $23,820 (interquartile range, $19,604-$29,958). Compared with the risk-standardized average, 17 hospitals (27.4%) had lower-than-expected costs, and 14 hospitals (22.6%) had higher-than-expected costs. At the facility level, the index PCI accounted for 83.1% of the total cost (range, 60.3%-92.2%), whereas hospitalization after PCI accounted for only 5.8% (range, 2.0%-12.7%) of the 30-day total cost. Facilities with higher hospitalization rates were not more expensive (Spearman ρ=0.16; 95% confidence interval, -0.09 to 0.39; P=0.21).In this national study, hospitalizations in the 30 day after PCI accounted for only 5.8% of 30-day cost, and facility-level cost was not correlated with hospitalization rates. This challenges the focus on reducing hospitalizations after PCI as an effective means of improving healthcare value. Opportunities remain to improve PCI value by reducing the variation in total cost of PCI without compromising patient outcomes.
Reply:
Authors: Pietro Lampertico, Enrico Galmozzi, Massimo Colombo
Journal: Hepatology (2012)

We fully agree with Dr. Sonneveld et al.'s interpretation of our study1 suggesting an interplay between response to interferon and rs12979860 polymorphisms in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B in Italy. The reason we omitted presenting data on an association between interleukin (IL)28B polymorphisms and HBV genotype was that more than 90% of the patients of Italian descent enrolled in the study carry the genotype D of HBV. Owing to the small sample size of the study, we thought it was impossible to evaluate predictors of response to interferon in relation to HBV genotype, yet to comply with Dr. Sonneveld et al.'s,2 we reanalyzed our results according to HBV genotype. IL28B stratification was 48% for CC, 41% for CT, and 11% for TT, the rates of end-of-treatment response, sustained response, and HBsAg clearance among the 93 genotype D patients being still significantly higher in CC than in non-CC carriers, i.e., 69% versus 44% (P = 0.014), 31% versus 12% (P = 0.028), and 29% versus 12% (P = 0.048). To obtain further insights into the association between interferon response and IL28B polymorphisms in our population, we expanded our investigation to the rs8099917 polymorphism of IL28B that was recently shown to refine the prediction of a response to interferon and ribavirin therapy among chronic hepatitis C patients carrying the CT genotype of rs12979860.3 In our study, the favorable rs8099917 TT genotype was found in 100% of the rs12979860 CC patients compared to 31% of CT and 10% of TT patients only. Among the 42 rs12979860 CT patients, off-therapy responses were significantly higher in the 13 rs8099917 TT than in the 29 rs8099917 TG patients, with a rate of sustained virological response of 23% versus 3%, P = 0.045 and of HBsAg loss of 23% versus 0%, P = 0.007. Taken together, our findings not only confirm the association between IL28B polymorphism of rs12979860 and response to interferon in genotype D patients with HBeAg-negative chronic hepatitis B, but, for the first time, provide evidence that the copresence of the rs8099917 SNP near IL28B may improve pretreatment prediction of response to interferon. Pietro Lampertico M.D., Ph.D.*, Enrico Galmozzi Ph.D.*, Massimo Colombo M.D.*, * "A.M. e A. Migliavacca" Center for the Study of Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy.