bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transfer of Low Dose Aspirin Into Human Milk
Authors: Datta Palika , Rewers-Felkins Kathleen , Kallem Raja Reddy , Baker Teresa , Hale Thomas W. 
Published: March 2017

Background: Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. Methods: In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography–tandem mass spectrometry. Results: Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Conclusion: Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.
Circulatory power and ventilatory power over time under goal‐oriented sequential combination therapy for pulmonary arterial hypertension
Authors: Hirashiki Akihiro , Adachi Shiro , Nakano Yoshihisa , Kamimura Yoshihiro , Shimokata Shigetake , Takeshita Kyosuke , Shimizu Atsuya , Toba Kenji , Murohara Toyoaki , Kondo Takahisa 
Published: March 2017

Many therapeutic options are available for patients with pulmonary arterial hypertension (PAH). However, little is known about the effects of sequential combination therapy on exercise capacity. Here we monitored exercise capacity by cardiopulmonary exercise testing (CPX) and observed the benefit of using a peak VO2 cutoff of 15 mL/kg/min to guide combination therapy. Thirty patients newly diagnosed with PAH were treated with goal‐oriented sequential combination therapy. Endothelin receptor antagonists (ERA) were the first‐line treatment, with phosphodiesterase type 5 inhibitors (PDE‐5i) as the preferred combination partner. The patients underwent cardiac catheterization at baseline and after 12 months and CPX at baseline and after three, six, and 12 months. Circulatory power (CP) was defined as the product of peak O2 uptake and peak systolic blood pressure (SBP); ventilatory power (VP) was defined as peak SBP divided by the minute ventilation–CO2 production slope. After 12 months, ERA had been administered to 100% of the study patients and PDE‐5i to 82%. Mean CP at baseline and after three, six, and 12 months was 1807, 2063, 2248, and 2245 mmHg·min/mL/kg, respectively, and mean VP was 2.93, 3.53, 4.16, and 3.68 mmHg, respectively. CP was greater after 6 months than at baseline (P = 0.047); VP was greater after three months than at baseline (P = 0.019) and further improved at six months compared with three months (P = 0.040). Therefore, repeated CPX assessment, including measurement of CP and VP, can provide useful information regarding the efficacy of goal‐oriented treatment for PAH.
Discordance in investigator-reported and adjudicated sudden death in TIOSPIR
Authors: Wise Robert A. , Kowey Peter R. , Austen George , Mueller Achim , Metzdorf Norbert , Fowler Andy , McGarvey Lorcan P. 
Published: March 2017

Accurate and consistent determination of cause of death is challenging in chronic obstructive pulmonary disease (COPD) patients. TIOSPIR (N=17 135) compared the safety and efficacy of tiotropium Respimat 5/2.5 µg with HandiHaler 18 µg in COPD patients. All-cause mortality was a primary end-point. A mortality adjudication committee (MAC) assessed all deaths. We aimed to investigate causes of discordance in investigator-reported and MAC-adjudicated causes of death and their impact on results, especially cardiac and sudden death.The MAC provided independent, blinded assessment of investigator-reported deaths (n=1302) and assigned underlying cause of death. Discordance between causes of death was assessed descriptively (shift tables).There was agreement between investigator-reported and MAC-adjudicated deaths in 69.4% of cases at the system organ class level. Differences were mainly observed for cardiac deaths (16.4% investigator, 5.1% MAC) and deaths assigned to general disorders including sudden death (17.4% investigator, 24.6% MAC). Reasons for discrepancies included investigator attribution to the immediate (e.g.myocardial infarction (MI)) over the underlying cause of death (e.g.COPD) and insufficient information for a definitive cause.Cause-specific mortality varies in COPD, depending on the method of assignment. Sudden death, witnessed and unwitnessed, is common in COPD and often attributed to MI without supporting evidence.
Psychological profile of individuals presenting with chronic cough
Authors: Hulme Katrin , Deary Vincent , Dogan Sian , Parker Sean M. 
Published: March 2017

Chronic refractory cough (CRC) is a common problem in respiratory clinics. Adverse effects on quality of life are documented in the literature, but relatively little is known about the underlying psychological factors in this patient population. We aimed to investigate the association of psychological factors with chronic cough, comparing CRC to explained cough and non-cough groups.67 patients attending a specialist cough clinic (CRC, n=25; explained cough, n=42) and 22 non-cough individuals participated. All participants completed the Hospital Anxiety & Depression Scale, Big Five Inventory (Personality), Chalder Fatigue Scale and Patient Health Questionnaire-15. Cough patients also completed the Illness Perception Questionnaire-Revised. Appropriate statistical analyses were used to compare participant groups.Chronic refractory coughers displayed significantly higher levels of anxiety, depression, fatigue and somatic physical symptoms than non-cough participants. Compared to explained coughers, there were higher depression and fatigue scores and significantly more negative illness representations (specifically, strong beliefs regarding negative consequences, lower illness coherence and higher emotional representations). “Explained” coughers reported significantly increased fatigue and somatic symptoms in comparison to non-coughers.The prevalence of fatigue, low mood, negative illness beliefs and increased physical symptom reporting should be considered in consultations and in developing novel interventions for CRC patients.
Survival results of a multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer (JACCRO GC-06).
Authors: Nishikawa Kazuhiro , Kimura Yutaka , Masuishi Toshiki , Kunisaki Chikara , Matsusaka Satoshi , Segawa Yoshihiko , Nakamura Masato , Sasaki Kinro , Nagao Narutoshi , Hatachi Yukimasa , Yuasa Yasuhiro , Asami Shinya , Takeuchi Masahiro , Furukawa Hiroshi , Fujii Masashi , Nakajima Toshifusa 
Published: March 2017

100 Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in Japan. In patients with HER-2 positive AGC, combined administration of fluoropyrimidine plus cisplatin and trastuzumab is the standard treatment. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. Especially, these disadvantages of cisplatin are noticeable in elderly patients. We have already reported the results of the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. In this time, we report the survival results of this study. Methods: Patients, 65 years or older, with HER-2 positive AGC received S-1 (80-120mg per day) orally on days 1-28 of a 42-day cycle and trastuzumab (first time: 8 mg/kg, from 2nd onward: 6 mg /kg) intravenously on day 1 of a 21-day cycle. Results: A total of 51 patients were enrolled. One patient was ineligible, one patient did not receive study treatment, therefore in the full analysis set of 49 patients, the median age was 71 years (range: 65-85) and ECOG PS was 0/1/2: 32/14/3. The confirmed RR (CR/PR/SD/PD: 2/18/21/8) was 40.8% (80% confidence interval (CI): 31.8-49.8%, 95% CI: 27.1-54.6%), and the null hypothesis was rejected. Median follow up period was 10.6 months. Median OS was 15.8 months (95%CI: 9.13-20.37). Median PFS was 5.1 months (95%CI: 3.78-5.55), and TTF was 4.0 months (95%CI: 3.09-5.39). Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects, as well as promising survival results in elderly patients with HER-2 positive AGC. Clinical trial information: 000007368.
Interim safety and clinical activity in patients (pts) with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma from a multicohort phase 1 study of ramucirumab (R) plus pembrolizumab (P).
Authors: Chau Ian , Bendell Johanna C. , Calvo Emiliano , Santana-Davila Rafael , Rodon Ahnert Jordi , Penel Nicolas , Arkenau Hendrik-Tobias , Yang Jing , Rege Jessicca , Mi Gu , Ferry David , Herbst Roy S. , Fuchs Charles S. 
Published: March 2017

102 Background: Angiogenesis and immunosuppression are hallmarks of tumor growth. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the tumor microenvironment. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02443324) enrolled pts with confirmed G/GEJ adenocarcinoma with prior progression on systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. PD-L1 was classified as positive (≥1%) or negative using the DAKO PD-L1 22C3 IHC pharmDx assay. Two dosing regimens were evaluated, Cohort A (R 8 mg/kg on Days 1&8) and Cohort B (R 10 mg/kg on Day 1), given with P 200 mg on Day 1 q3W. The primary objective was to assess safety and tolerability of adding R to P; preliminary efficacy will be examined. Results: As of 23-Jun-2016, 40 G/GEJ pts have been enrolled (Cohort A: n=23; Cohort B: n=17). First pt treated in Cohorts A and B were on 29-Feb-2016 and 26-Oct-2015, respectively. The median age was 59 y, 75% were male, 65% had ECOG PS of 1, 48% were PD-L1 positive, and 70% received study treatment as third or subsequent regimen. Median duration of treatment was 2.1 mo and 4.1 mo for Cohort A and B, respectively. All grades treatment-related AEs (TRAE) occurred in 31 (78%) pts and similar between cohorts; TRAEs in ≥10% of pts were fatigue (30%), infusion related reaction (12.5%), decreased appetite (12.5%), pruritus (10%), maculopapular rash (10%), and hypertension (10%). Ten (25%) pts had grade 3-4 TRAEs, most commonly colitis (7.5%) and hypertension (7.5%). One treatment-related death occurred (pneumocystis pneumonia and pulmonary sepsis). Preliminary efficacy data showed 3 of 40 (7.5%) pts (PD-L1 negative, n=1; PD-L1 positive, n=2) have responded (1 confirmed and 2 unconfirmed PR) to treatment with a 45% disease control rate. Median PFS was 2.10 mo (95% CI, 1.18 to 4.04) and 2.60 mo (1.38, NR) for Cohorts A and B, respectively. Fifteen (37.5%) pts, including all responders, remain on treatment. Conclusions: R+P generated no new safety signals and demonstrated antitumor activity in pts with previously treated advanced G/GEJ adenocarcinoma. Clinical trial information: NCT02443324.
Upfront surgery, neoadjuvant, and definitive chemoradiation for clinical T2N0 esophageal adenocarcinoma: A propensity score matched analysis from the National Cancer Database analysis.
Authors: Shridhar Ravi , Huston Jamie , Meredith Kenneth L 
Published: March 2017

103 Background: To compare overall survival (OS) of T2N0 esophageal adenocarcinomas treated with either upfront surgery (US), neoadjuvant chemoradiation (NCR), or definitive chemoradiation (DCR) from the National Cancer Database (NCDB). Methods: The NCDB was accessed to identify patients with T2N0 esophageal adenocarcinoma treated between 2004-2013 with either US, NCR, or DCR. NCR and DCR patients were included if they were treated with a radiation dose between 45-50.4 Gy and received chemotherapy. Propensity score matching (PSM) was performed against age and tumor length. Results: After PSM, 446 patients (US 98; NCR 203; DCR 145) were included in the analysis. There was no difference in age, tumor length, and grade. Clinical staging in US patients was accurate pathologically in 32.6% of patients. Median and 5 year OS for US, NCR, and DCR patients was 42.5 months and 40%, 48.5 months and 48%, and 22.9 months and 20%, respectively (p<0.001). There was no difference in OS based on response to NCR compared to US. NCR was associated with improved OS in patients with tumors >3 cm compared to US (median OS 43.8 versus 36.4 months; p=0.01). There was a trend toward improved OS with NCR in high grade tumors compared to US. UVA and MVA of OS revealed that DCR was associated with worse survival. Conclusions: Clinical staging for T2N0 esophageal adenocarcinoma continues to remain highly inaccurate. There was no difference in OS between US and NCR, however, improved OS was seen in NCR patients with tumors >3 cm.
Risk of peritoneal carcinomatosis in localized gastric adenocarcinoma patients who undergo preoperative therapy and attempted surgery.
Authors: Mizrak Kaya Dilsa , Nogueras-Gonzalez Graciela M. , Harada Kazuto , Blum Murphy Mariela A. , Das Prajnan , Minsky Bruce D. , Estrella Jeannelyn , Lin Quan , Ghazanfari Amlashi Fatemeh , Lee Jeffrey H , Weston Brian , Bhutani Manoop S. , Wu Carol C , Matamoros Aurelio , Sagebiel Tara L. , Mansfield Paul F. , Badgwell Brian D. , Ajani Jaffer A. 
Published: March 2017

104 Background: Positive peritoneal cytology (+PCyt) or gross peritoneal carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b GACs. The natural history of GAC patients who have baseline –PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC. Methods: We analyzed 178 GAC patients with -PCyt at baseline who were followed postoperatively. Results: Of 178 patients who went to surgery after preoperative therapy, surgery in 14 patients (7.9%) was aborted due to GPC in 13 patients, and liver metastases in 1. We then analyzed 164 patients who had an R0 resection. The median follow-up duration was 3.4 (0.6-18) years. The rate of subsequent GPC was 13.4%, (22/164 patients) and the median time to GPC was 15.6 months. The median overall survival (OS) after GPC was only 7.1 months (95% CI: 0.4-17.9 months). Various clinical variables were related with GPC after an R0 resection (Table 1). The 5-year OS rate for patients without subsequent GPC was 75%. Conclusions: Even with baseline –PCyt, subsequent risk for GPC is ~20% in the best group of localized GAC patients. Patients who do not develop GPC have an excellent (75%) OS rate. Further research is warranted to identify patients at high risk of subsequent GPC. [Table: see text]
New tyrosine kinase inhibitors in the treatment of imatinib resistant GIST: An updated meta-analysis.
Authors: Pendola Fiorella , Guirguis John , Ripat Caroline , Yakoub Danny , Hoffman James Edward , Dabage Nemer 
Published: March 2017

110 Background: Primary or secondary resistance to Imatinib, convolutes the control of Gastrointestinal Stromal Tumors (GIST). We aimed to evaluate clinical outcomes of new tyrosine kinase inhibitors (TKIs) in the treatment of Imatinib resistant GIST. Methods: Online database search of PubMed, MEDLINE, EMBASE, SCOPUS, COCHRANE, and GOOGLE SCHOLAR was performed (2000– Present); key bibliographies were reviewed. Studies comparing patients with Imatinib resistant GIST who were treated with placebo versus new generation TKIs (Regorafenib, Sunitinib, Nilotinib). Primary outcomes were overall and progression free survival (OS, PFS), secondary outcomes include the most common side effects described in trials using new TKIs. Meta-analysis was conducted using Statistical Analysis System (SAS) software. Relative risks with the corresponding 95% confidence intervals (CI) by random effects models of pooled data were calculated. Study quality was assessed using JADAD scoring system. Results: Out of 16 studies, 4 studies met our selection criteria including 825 patients in total; 553 treated with new TKIs and 272 were given placebo (control group). Median age was 57.85 years. Meta-analysis of included data showed significantly improved PFS in the new TKIs group (HR = 0.336, 95% CI 0.208-0.542, p < 0.001.) Similar trend but without statistically significant difference was seen in OS (HR = 0.836, 95% CI 0.682-1.026, p = 0.086). Incidence of hypertension was found to be significantly higher in the new TKIs group (RR = 2.903, 95% CI 1.800-4.681, p < 0.001); the same effect was observed in development of hand foot syndrome (RR = 4.818, 95% CI 2.723-8.525, p < 0.001) and diarrhea (RR = 5.341, 95% CI 3.074-9.281, p < 0.001). Conclusions: New generation of TKIs significantly improved PFS compared with placebo in patients with Imatinib resistant GIST. However new TKIs have increased secondary side effects. Randomized controlled trials are needed to evaluate longer term outcomes of these treatments.
Phase II study of S-1 plus oxaliplatin (OX) at dose of 130 mg/m2 (SOX130) in Japanese patients (pts) with advanced gastric cancer (AGC).
Authors: Kito Yosuke , Machida Nozomu , Hamauchi Satoshi , Tsushima Takahiro , Todaka Akiko , Yokota Tomoya , Yamazaki Kentaro , Fukutomi Akira , Onozawa Yusuke , Tsuji Kunihiro , Doyama Hisashi , Haraguchi Yutaka , Nakashima Koji , Kunieda Kenji , Taku Keisei , Mori Keita , Yasui Hirofumi 
Published: March 2017

112 Background: The phase III G-SOX trial had adopted SOX100 due to high incidence of thrombocytopenia in the previous phase I/II study, and failed to demonstrate the non-inferiority of SOX100 to S-1 plus cisplatin in chemotherapy-naïve Japanese pts with AGC. However, OX 130 mg/m2 has been approved for AGC in Japan since Sep 2014 on the evidence of the REAL-2 trial. Therefore, we conducted a study to evaluate the feasibility of SOX130 in Japanese AGC pts. Methods: This is a single-arm, open-label, multicenter, phase II study. Pts with unresectable or recurrent adenocarcinoma of stomach, no prior chemotherapy and ECOG PS 0 or 1 were treated with SOX130 (S-1 80-120 mg/day according to BSA for 2 weeks, OX 130 mg/m2 on day 1, every 3 weeks). The primary endpoint was the 3-cycle completion rate, defined as the proportion of pts who receive at least 80% of the planned OX dose for the first 3-cycle. We set the threshold 3-cycle completion rate at 50% and the expected rate at 75%. A sample size of 23 pts was needed with 80% power at a 5% α-level (one-sided). Results: From April 2015 to June 2016, 25 pts were enrolled. Pts’ characteristics were as follows: median age 64.5 years (range, 32-76), male/female 21/4, PS 0/1 15/10, unresectable/recurrent 21/4, and intestinal/diffuse 7/18. The 3-cycle completion rate was 72.0% (90% CI 53.8-86.1%). Among the 12 pts with measurable lesions, objective response rate and disease control rate were 58.3% and 83.3%, respectively. With a median follow-up period of 5.2 months, median progression-free survival was 7.5 months. Grade 3 adverse events were anorexia (n = 5), anemia (n = 3), thrombocytopenia (n = 2), neutropenia (n = 1) and nausea (n = 1). No treatment-related death was observed. Conclusions: SOX130 could be a first-line treatment option even in Japanese AGC pts. Clinical trial information: UMIN000016973.
Outcomes of definitive radiotherapy (dRT) and chemo-radiotherapy (dCRT) for loco-regionally confined (LRC) adenocarcinoma (ACA) of the esophagus and gastro-esophageal junction (E/GEJ).
Authors: Karivedu Vidhya , McNamara Michael J. , Rybicki Lisa A. , Al taii Haider , Sohal Davendra , Rodriguez Cristina P. , Videtic Gregory M.M. , Stephans Kevin L. , Ives Denise I. , Bodmann Joanna , Adelstein David J. 
Published: March 2017

114 Background: Surgery is the cornerstone of curative intent therapy for patients with ACA of the E/GEJ. Many patients (pts) with LRC disease are medically unsuitable for resection, and thus alternative treatment strategies are required. Definitive CRT is a standard of care for esophageal squamous cell carcinoma, but less is known regarding the outcomes for ACA of the E/GEJ. Methods: Through the Cleveland Clinic tumor registry, and under an IRB approved protocol, pts with LRC (clinical stage I-III, AJCC 7th) ACA of the E/GEJ treated with either dRT or dCRT between 7/04 and 12/14 were identified. Overall survival (OS) from the date of diagnosis was the primary endpoint. In univariate analysis, Cox proportional hazard analysis was used to identify risk factors for mortality. On multivariable analysis, stepwise Cox proportional hazard analysis with variable entry criterion p≤0.10 and variable retention criteria p≤0.05 was used to identify risk factors for mortality. Results: From 7/04 to 12/14, 155 pts received definitive non-operative treatment (103 dCRT, 52 dRT). Clinical stage I disease was present in 20 (13.2%); stage II in 40 (26.5%) and stage III in 91 (60.3%) of the pts. Pts who received dCRT were younger (67 v 74 years, p<0.001) and had more advanced clinical stage (p=0.026). Loco-regional recurrence / persistence was the predominant form of treatment failure occurring in 60% of pts (dCRT 54.3%, dRT 71.2%, p=0.044). With a median follow-up of 34.9 months (range 2.0-107.1), the median OS was 17.3 months (15.6m dCRT, 19.8m dRT, p=0.40) and the projected 5 year OS was 11.5% (16.1% dCRT, 4.0% dRT, p = 0.030). On univariable and multivariable analysis, a worse ECOG performance status, increasing clinical T descriptor, and increasing clinical N descriptor were prognostic for a worse OS. After adjusting for these variables, dRT was associated with a worse OS [dRT/dCRT HR 1.79 (1.20-2.68) p=0.005]. Conclusions: Definitive RT/CRT for LRC ACA of the E/GEJ is associated with poor OS. Long-term survival is nonetheless possible in a small number of pts and appears more likely after dCRT.