bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation
Authors: Ott Christian , Jumar Agnes , Striepe Kristina , Friedrich Stefanie , Karg Marina V. , Bramlage Peter , Schmieder Roland E. 
Published: February 2017

Abstract
Background
The sodium–glucose cotransporter 2 inhibitor, dapagliflozin, has been shown to improve diabetic control and reduce blood pressure in patients with type 2 diabetes mellitus. Its effects on micro- and macrovascular structure and function have not yet been reported.

Methods
This was a prospective, single-centre, placebo-controlled, double-blind, randomised crossover phase IIIb study conducted between March 2014 and February 2015. After a 4-week run-in/washout phase, patients (N = 59) received 6 weeks of either dapagliflozin 10 mg or placebo once daily. They then underwent a 1-week washout before crossing over to the other treatment. Changes in retinal capillary flow (RCF) and arteriole remodelling were evaluated using scanning laser Doppler flowmetry, while micro- and macrovascular parameters in the systemic circulation were assessed using pulse wave analysis.

Results
Six weeks of dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values. RCF decreased from 324 AU at baseline to 308 AU after treatment with dapagliflozin (p = 0.028), while there was little difference after the placebo (318 AU; p = 0.334). Furthermore, the arteriole remodelling that was seen after the placebo phase was not evident after the dapagliflozin phase. Central systolic and diastolic blood pressure values were significantly lower after 6 weeks of dapagliflozin, by 3.0 and 2.2 mmHg, respectively (p = 0.035 and 0.020, respectively vs. baseline).

Conclusions
Six weeks of dapagliflozin treatment resulted in numerous beneficial effects. In addition to achieving superior diabetes control and blood pressure, parameters associated with the early stages of vascular remodelling were also improved.
Trial registrationhttp://www.clinicaltrials.gov (NCT02383238)
Osteogenesis evaluation of duck’s feet-derived collagen/hydroxyapatite sponges immersed in dexamethasone
Authors: Kook Yeon Ji , Lee Dae Hoon , Song Jeong Eun , Tripathy Nirmalya , Jeon Yoo Shin , Jeon Ha Yan , Oliveira Joaquim M. , Reis Rui L. , Khang Gilson 
Published: February 2017

Abstract

Background
The aim of this study was to investigate the osteogenesis effects of DC and DC/HAp sponge immersed in without and with dexamethasone.

Methods
The experimental groups in this study were DC and DC/HAp sponge immersed in without dexamethasone (Dex(−)DC and Dex(−)-DC/HAp group) and with dexamethasone (Dex(+)-DC and Dex(+)-DC/HAp group). We characterized DC and DC/HAp sponge using compressive strength, scanning electron microscopy (SEM). Also, osteogenic differentiation of BMSCs on sponge (Dex(−)DC, Dex(−)-DC/HAp, Dex(+)-DC and Dex(+)-DC/HAp group) was assessed by SEM, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay, alkaline phosphatase (ALP) activity assay and reverse transcription-PCR (RT-PCR).

Results
In this study, we assessed osteogenic differentiation of BMSCs on Duck’s feet-derived collagen (DC)/HAp sponge immersed with dexamethasone Dex(+)-DC/HAp. These results showed that Dex(+)-DC/HAp group increased cell proliferation and osteogenic differentiation of BMSCs during 28 days.

Conclusion
From these results, Dex(+)-DC/HAp can be envisioned as a potential biomaterial for bone regeneration applications.
Dose, Response, and Survival in Metastatic Mammary Cancer
Authors: Kagan A. Robert 
Published: February 2017

To the Editor: Congratulations to Hryniuk and Bush in their effort to make sense out of many different chemotherapy regimens. However, in my opinion, I think they interpret their results too narrowly. For example, in Fig 2 and especially Fig 4, a straight line parallel to the ordinate at 0.6 fits the data as well as a line with a slope. In Fig 5, I am led by the discussion to accept a line from a median survival time (MST) of 10 months to an MST of 20 months, as the CR plus PR percent is increased from 20% to 80%. A line parallel to the abscissa at an MST of 15 months fits the data as well. If the lines drawn through the data have slopes, then the authors are correct in postulating increased dose intensity from 0.6 to 1.0+ indicates increased responses and increased survival. On the other hand, parallel lines drawn through the data give an alternate conclusion, namely that a threshold must be reached to achieve maximum benefit and doses above the threshold dose achieve very little. Accepting the data points by Hryniuk and Bush without criticism, how do we know what line best fits their compilation of data, a straight line or a line with a slope?
Dose Intensity in Chemotherapy
Authors: Tonkin Katia , Tannock Ian 
Published: February 2017

To the Editor: In a recent article, Hryniuk and Bush have established a strong correlation between dose intensity of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy, and the rate of tumor response in patients with metastatic breast cancer. They also observed a significant correlation between rate of tumor response and median survival time (r = .66, P < .001). The authors were careful to avoid the conclusion that there was a direct correlation between dose intensity and median survival, but it is surprising that they did not examine this more important relationship directly. We have used data provided in their paper to test for correlation between median survival time and dose intensity for patients receiving CMF chemotherapy, and find little evidence for a direct relationship (r = .25, P = .27—two-tailed Student's t test). Moreover, if the studies are weighted according to the number of patients in them, the correlation coefficient is even lower (r = .14, P = .50—two-tailed Student's t test). Unfortunately, metastatic breast cancer is not cured by chemotherapy, and appropriate endpoints are those of palliation, namely quantity and quality of survival. Quality of survival cannot easily be addressed in a retrospective review, but increasing dose intensity has the capability both to improve quality of life by ameliorating symptoms of disease, and to decrease it by adding toxicity. Factors such as sites of metastases and performance status of patients are known to influence duration of survival and could mask a relationship with dose intensity. However, the data reviewed by Hryniuk and Bush do not provide evidence for a relationship between dose of chemotherapy and survival. A prospective randomized trial is in progress at our institution that addresses the relationship between dose intensity of CMF chemotherapy and both quantity and quality of survival for patients with metastatic breast cancer. In the absence of results from this and other prospective trials that address the dose-response effect of chemotherapy in palliation, one should not assume that more is better.
A Randomized Trial Comparing Cisplatin Plus Cyclophosphamide Versus Cisplatin, Doxorubicin, and Cyclophosphamide in Advanced Ovarian Cancer
Authors: Conte P.F. , Bruzzone M. , Chiara S. , Sertoli M.R. , Daga M.G. , Rubagotti A. , Conio A. , Ruvolo M. , Rosso R. , Santi L. , Carnino F. , Cottini M. , Mossetti C. , Guercio E. , Gatti M. , Siliquini P.N. , Prelato M.L. , Durando C. , Giaccone G. , Calciati A. , Farinini D. , Centonze M. , Rugiati S. , Parodi G. , Messineo M. , Storace A. , Bernardini G. , Misurale F. , Alessandri S. , Casini M. , Ragni N. , Foglia G. , Bentivoglio G. , Pescetto G. 
Published: February 2017

In the article by Conte et al, "A Randomized Trial Comparing Cisplatin Plus Cyclophosphamide Versus Cisplatin, Doxorubicin, and Cyclophosphamide in Advanced Ovarian Cancer" (Journal of Clinical Oncology 4:965–971, 1986), an error was made in the abstract on page 965 that altered the meaning of a sentence. The correct sentence appears below. After primary surgery, 125 patients with epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] 1c + IIb + IIc = 22 patients, FIGO III = 82 patients, FIGO IV = 21 patients) were randomly allocated to receive PC (cisplatin 50 mg/m2 + cyclophosphamide 600 mg/m2 on day 1 every 28 days) or PAC (PC + doxorubicin 45 mg/m2).
A Phase I Clinical and Pharmacokinetic Study of Carboplatin and Autologous Bone Marrow Support
Authors: Shea Thomas C. , Flaherty Mary , Elias Anthony , Eder Joseph P. , Antman Karen , Begg Colin , Schnipper Lowell , Frei Emil , Henner William D. 
Published: February 2017

The key to Fig 1 in the report by Shea et al published in the May issue (J Clin Oncol 7:651–661, 1989) contained several errors. It is reprinted here correctly with the figure in its entirety. Please see the PDF for Figure.
A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy.
Authors: Antman K , Ayash L , Elias A , Wheeler C , Hunt M , Eder J P , Teicher B A , Critchlow J , Bibbo J , Schnipper L E 
Published: February 2017

PURPOSE The study was designed to determine the duration of complete response (CR) for patients with unresectable or metastatic breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) while responding to conventional-dose therapy. METHODS Eligibility criteria included histologically documented metastatic or unresectable breast cancer, at least a partial response (PR) to conventional-dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m3, and physiologic age between 18 and 55 years. Patients with inadequate renal, hepatic, pulmonary, and/or cardiac function or tumor involvement of marrow or CNS were excluded. Cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 were given by continuous infusion over 4 days. After recovery, sites of prior bulk disease were to be radiated or resected if feasible. RESULTS Of 29 registered patients, one died of toxicity (3%; hemorrhage). CRs and PRs continued a median of 16 and 5 months after transplant, respectively (26 and 9 months from initiation of chemotherapy for metastatic disease). Of 10 patients transplanted in CR, four have not progressed at 17 to 31 months after transplantation (25 to 43 months after beginning standard-dose therapy). One of four patients with uptake on bone scan as their only sites of residual disease before transplant and one of three who converted from PR to CR with transplant have not progressed at 27 and 29 months, respectively, after transplant. CONCLUSIONS CTCb is an intensification regimen with a low mortality that delivers a significantly increased dose of agents with known activity at conventional doses in breast cancer. Although the duration of PR is short as expected, CRs appear to be durable.
A method of predicting adult height and obesity in long-term survivors of childhood acute lymphoblastic leukemia.
Authors: Schell M J , Ochs J J , Schriock E A , Carter M 
Published: February 2017

PURPOSE Short stature and obesity have been reported among long-term survivors of childhood acute lymphocytic leukemia (ALL). We examined factors that contribute to these adverse sequelae. PATIENTS AND METHODS Serial height and weight measurements were analyzed for 91 long-term survivors who were treated for ALL between 1967 and 1975 at a single institution. These patients were all younger than 12 years at diagnosis, were in continuous complete remission, had reached final height, and had height and weight measurements within 1 year of age 18 years. They had received craniospinal (n = 33) or cranial irradiation (n = 58) to total doses of 24 Gy as CNS prophylaxis. Standard deviation scores (SDS) were used to reflect the deviation of height and weight measurements from population means, and the body mass index (BMI; weight divided by height squared) was used in assessing obesity at age 18 years. RESULTS Short stature (less than fifth percentile) was seen in 41 patients (45%), and obesity (BMI greater than or equal to 24 kg/m2) in 35 (38%). Regression formulae were developed that explain 65% and 62% of the variability in patient height and BMI, respectively. CONCLUSIONS Risk factors were identified for abnormally short stature, which was defined to be a decrease of 1.5 SDS in height from diagnosis to age 18 years. These factors include younger age and above-average height for age at diagnosis (height SDS greater than 0), craniospinal irradiation, and greater decrease in height SDS during antileukemic therapy. Risk factors for obesity at age 18 years include weight SDS greater than 0 and greater than height SDS at 1 year after the end of chemotherapy.
The incidence of second primary tumors in long-term survivors of small-cell lung cancer.
Authors: Heyne K H , Lippman S M , Lee J J , Lee J S , Hong W K 
Published: February 2017

PURPOSE AND METHODS A review of 446 patients who were enrolled consecutively in small-cell lung cancer (SCLC) protocols was performed to identify in long-term survivors the frequency of new primary tumors and their clinical impact. RESULTS Forty-seven patients (10.5%) were identified to be free of disease at 2 years. Second primary tumors (SPTs) were diagnosed in 14 patients. The overall risk for developing an SPT was 10.3% per person-year. Actuarial risk at 8 years was 50.3% for an SPT. CONCLUSIONS In this review, SCLC showed one of the highest incidences of SPTs reported in aerodigestive tract malignancies. A long-term survivor was more likely to have an SPT than a relapse of SCLC. Consequently, the odds of death from an SPT compared with that from a relapse increased sharply from 1:13 within 4 years from diagnosis to 8:1 afterwards. Long-term survivors of SCLC would be excellent candidates for chemoprevention trials.
Improved palliation of cerebral metastases in epithelial ovarian cancer using a combined modality approach including radiation therapy, chemotherapy, and surgery.
Authors: Rodriguez G C , Soper J T , Berchuck A , Oleson J , Dodge R , Montana G , Clarke-Pearson D L 
Published: February 2017

PURPOSE Recent reports suggest an increasing incidence of CNS metastases in patients with ovarian cancer. We reviewed our experience in the management of brain metastases from ovarian carcinoma and merged our results with those of several other series reported in the literature to determine prognostic factors and the role of chemotherapy, radiation therapy, and surgery. PATIENTS AND METHODS From 1977 to 1990, 15 of 795 patients who were treated for epithelial ovarian cancer at Duke University developed brain metastases. Fourteen of the patients were treated for their brain metastases; this included radiation therapy (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all three treatment modalities (three). A meta-analysis was performed that combined the data from the current series with those of several recent clinical series that reviewed patients with brain metastases from ovarian carcinoma (67 patients total) to elucidate the impact of treatment and extent of disease on survival. RESULTS In the current series, median survival (MS) after the diagnosis of brain metastases was 9 months. For the combined series, MS was 5 months. Thirteen patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7 months), 10 patients who were treated with RT and surgery (MS, 10 months), and nine patients who were treated with all three modalities (MS, 16.5 months) had significantly longer survival than 19 patients who were treated with RT alone (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate analysis, the only variable that provided prognostic information was treatment, namely the addition of systemic chemotherapy or surgery to RT for the treatment of brain metastases. CONCLUSION Multimodal treatment of patients with brain metastases from ovarian cancer can result in significant palliation.
Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's disease: the experience of the French Society of Pediatric Oncology.
Authors: Oberlin O , Leverger G , Pacquement H , Raquin M A , Chompret A , Habrand J L , Terrier-Lacombe M J , Bey P , Bertrand Y , Rubie H 
Published: February 2017

PURPOSE With the aim of decreasing undesirable side effects of therapy, we investigated the reduction of both chemotherapy and radiation therapy (RT) in children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy) after good response to chemotherapy. PATIENTS AND METHODS A French national study began in 1982 that included 238 pediatric patients with Hodgkin's disease. Initial staging was clinical and without laparotomy. In patients with localized disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP. Patients with more advanced disease (IB-IIB-III-IV) received three courses of MOPP that was alternated with three courses of ABVD. All of the patients who achieved a good remission after chemotherapy were administered 20 Gy RT, which was limited to the initially involved areas for localized disease, and encompassed the paraaortic nodes and the spleen as well for more advanced stages. When a good remission was not obtained, 40 Gy RT was administered. RESULTS At the completion of chemotherapy, 227 patients (97%) were considered good responders, whereas 11 did not achieve a good remission. With a median follow-up of 6 years, the 6-year actuarial survival was 92% and the disease-free survival was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV patients was discontinued because of poor results. CONCLUSIONS Present findings indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid therapeutic approach in the vast majority of children with Hodgkin's disease.
High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.
Authors: Lazarus H M , Crilley P , Ciobanu N , Creger R J , Fox R M , Shina D C , Bulova S I , Gucalp R , Cooper B W , Topolsky D 
Published: February 2017

PURPOSE We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).
Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with autologous bone marrow rescue in lymphomas and solid tumors.
Authors: Wilson W H , Jain V , Bryant G , Cowan K H , Carter C , Cottler-Fox M , Goldspiel B , Steinberg S M , Longo D L , Wittes R E 
Published: February 2017

PURPOSE High-dose chemotherapy produces durable disease-free remissions in a minority of patients with resistant lymphomas and solid tumors. In an attempt to improve on the available regimens, ifosfamide, carboplatin, and etoposide (ICE) were selected for a new high-dose regimen because of their favorable spectrum of nonhematopoietic toxicity and evidence of synergy in in vitro systems. PATIENTS AND METHODS Forty-one patients with drug-resistant Hodgkin's and non-Hodgkin's lymphomas, and breast and testicular cancers were entered onto a phase I and II trial of a single course of ICE with autologous bone marrow rescue. Before transplantation, all patients received combination chemotherapy until maximal tumor response was achieved. RESULTS Patients received total doses of ifosfamide from 10 to 18 g/m2, carboplatin from 0.9 to 1.98 g/m2, and etoposide from 0.6 to 1.5 g/m2 administered during a 4-day period, with a maximum-tolerated dose (MTD) of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 1.5 g/m2. The dose-limiting toxicities included irreversible renal, cardiac, and CNS dysfunction. There were three toxic deaths (7%), and all occurred above the MTD. Thirteen patients who were treated at the MTD tolerated the regimen well; reversible renal dysfunction and grade 2 mucositis commonly were observed. Of 23 heavily pretreated patients with persistent disease at the time of transplant, 10 (43%) achieved complete remissions (CRs) and 11 (48%) achieved partial remissions (PRs). Hodgkin's and non-Hodgkin's lymphoma patients who were treated at or below the MTD had a median potential follow-up of 11.9 months, and 12-month progression-free survivals of 62% and 48%, respectively. CONCLUSION High-dose ICE with bone marrow rescue was well tolerated with a high response rate, and should be considered for further testing.