bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of candidemia and invasive candidiasis in the intensive care unit: post hoc analysis of a randomized, controlled trial comparing micafungin and liposomal amphotericin B
Authors: Dupont Bertrand F , Lortholary Olivier , Ostrosky-Zeichner Luis , Stucker Flavie , Yeldandi Vijay 
Published: October 2009

Abstract
Introduction
Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients.

Methods
A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects ≤ 40 kg) versus liposomal amphotericin B (3 mg/kg/day). Subgroups were defined according to the type of ward on the first day of treatment: intensive care unit (ICU) or non-ICU. Multivariate regression was performed to identify factors associated with treatment success at end of therapy and all-cause mortality at days 8 and 30.

Results
In non-ICU subjects, treatment success was significantly higher for micafungin versus liposomal amphotericin B (85% (n = 108/127) versus 72.1% (n = 98/136); P = 0.0113). However, for ICU subjects, treatment success rates for micafungin versus liposomal amphotericin B were similar (62.5% (n = 75/120) versus 66.4% (n = 73/110); P = 0.5828). Overall, treatment success was significantly lower in ICU subjects compared with non-ICU subjects (64.3% (n = 148/230) versus 78.3% (n = 206/263); P = 0.0006). Multivariate regression analysis revealed a lower likelihood of treatment success for: ICU versus non-ICU subjects; persistent neutropenia; and high versus low Acute Physiology and Chronic Health Evaluation (APACHE) II scores. However, when interactions between potential explanatory factors were included in the analysis model, ICU status no longer emerged as a significant associated variable but the association between APACHE II score and treatment outcome remained. Further analyses indicated that the likelihood of mortality at day 8 and day 30 was lower for subjects with lower APACHE II scores. Renal function was significantly better in micafungin versus liposomal amphotericin B subjects: a difference (liposomal amphotericin B - micafungin in mean peak change in estimated glomerular filtration rate (ml/minute/1.73 m2) of -18.2 (P < 0.0001) and -17.7 (P = 0.0124) in non-ICU and ICU subjects, respectively.

Conclusions
Overall, ICU subjects had lower treatment success rates than non-ICU subjects for both liposomal amphotericin B and micafungin. Multivariate regression after controlling for potential confounding factors suggested the APACHE II score remained a potential explanatory factor associated with treatment success, mortality at day 8, and mortality at day 30.

Trial registration
Post hoc analysis - clinicaltrials.gov trial NCT00106288.
Effects of positive end-expiratory pressure on respiratory function and hemodynamics in patients with acute respiratory failure with and without intra-abdominal hypertension: a pilot study
Authors: Krebs Joerg , Pelosi Paolo , Tsagogiorgas Charalambos , Alb Markus , Luecke Thomas 
Published: October 2009

Abstract
Introduction
To investigate the effects of positive end-expiratory pressure (PEEP) on respiratory function and hemodynamics in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) with normal intra-abdominal pressure (IAP < 12 mmHg) and with intra-abdominal hypertension (IAH, defined as IAP ≥ 12 mmHg) during lung protective ventilation and a decremental PEEP, a prospective, observational clinical pilot study was performed.

Methods
Twenty patients with ALI/ARDS with normal IAP or IAH treated in the surgical intensive care unit in a university hospital were studied. The mean IAP in patients with IAH and normal IAP was 16 ± 3 mmHg and 8 ± 3 mmHg, respectively (P < 0.001). At different PEEP levels (5, 10, 15, 20 cmH2O) we measured respiratory mechanics, partitioned into its lung and chest wall components, alveolar recruitment, gas-exchange, hemodynamics, extravascular lung water index (EVLWI) and intrathoracic blood volume index (ITBVI).

Results
We found that ALI/ARDS patients with IAH, as compared to those with normal IAP, were characterized by: a) no differences in gas-exchange, respiratory mechanics, partitioned into its lung and chest wall components, as well as hemodynamics and EVLWI/ITBVI; b) decreased elastance of the respiratory system and the lung, but no differences in alveolar recruitment and oxygenation or hemodynamics, when PEEP was increased at 10 and 15cmH2O; c) at higher levels of PEEP, EVLWI was lower in ALI/ARDS patients with IAH as compared with those with normal IAP.

Conclusions
IAH, within the limits of IAP measured in the present study, does not affect interpretation of respiratory mechanics, alveolar recruitment and hemodynamics.
Defining the chromatin signature of inducible genes in T cells
Authors: Lim Pek S , Hardy Kristine , Bunting Karen L , Ma Lina , Peng Kaiman , Chen Xinxin , Shannon Mary F 
Published: October 2009

Abstract
Background
Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation.

Results
To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation.

Conclusions
These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation.
Comparison of Iodine-123 Metaiodobenzylguanidine (MIBG) Scan and [18F]Fluorodeoxyglucose Positron Emission Tomography to Evaluate Response After Iodine-131 MIBG Therapy for Relapsed Neuroblastoma
Authors: Taggart Denah R. , Han Myo M. , Quach Alekist , Groshen Susan , Ye Wei , Villablanca Judith G. , Jackson Hollie A. , Mari Aparici Carina , Carlson David , Maris John , Hawkins Randall , Matthay Katherine K. 
Published: October 2009

Purpose Children with relapsed neuroblastoma have poor survival. It is crucial to have a reliable method for evaluating functional response to new therapies. In this study, we compared two functional imaging modalities for neuroblastoma: metaiodobenzylguanidine (MIBG) scan for uptake by the norepinephrine transporter and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake for glucose metabolic activity. Patients and Methods Patients enrolled onto a phase I study of sequential infusion of iodine-131 (131I) MIBG (NANT-2000-01) were eligible for inclusion if they had concomitant FDG-PET and MIBG scans. 131I-MIBG therapy was administered on days 0 and 14. For each patient, we compared all lesions identified on concomitant FDG-PET and MIBG scans and gave scans a semiquantitative score. Results The overall concordance of positive lesions on concomitant MIBG and FDG-PET scans was 39.6% when examining the 139 unique anatomic lesions. MIBG imaging was significantly more sensitive than FDG-PET overall and for the detection of bone lesions (P < .001). There was a trend for increased sensitivity of FDG-PET for detection of soft tissue lesions. Both modalities showed similar improvement in number of lesions identified from day 0 to day 56 scan and in semiquantitative scores that correlated with overall response. FDG-PET scans became completely negative more often than MIBG scans after treatment. Conclusion MIBG scan is significantly more sensitive for individual lesion detection in relapsed neuroblastoma than FDG-PET, though FDG-PET can sometimes play a complementary role, particularly in soft tissue lesions. Complete response by FDG-PET metabolic evaluation did not always correlate with complete response by MIBG uptake.
Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
Authors: Witzig Thomas E. , Wiernik Peter H. , Moore Timothy , Reeder Craig , Cole Craig , Justice Glen , Kaplan Henry , Voralia Michael , Pietronigro Dennis , Takeshita Kenichi , Ervin-Haynes Annette , Zeldis Jerome B. , Vose Julie M. 
Published: October 2009

PurposeLenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL).Patients and MethodsPatients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety.ResultsForty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively).ConclusionOral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.
Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Authors: Schultz Kirk R. , Bowman W. Paul , Aledo Alexander , Slayton William B. , Sather Harland , Devidas Meenakshi , Wang Chenguang , Davies Stella M. , Gaynon Paul S. , Trigg Michael , Rutledge Robert , Burden Laura , Jorstad Dean , Carroll Andrew , Heerema Nyla A. , Winick Naomi , Borowitz Michael J. , Hunger Stephen P. , Carroll William L. , Camitta Bruce 
Published: October 2009

Purpose Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph− ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) –identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT.
Longitudinal Cohort Study of Risk Factors in Cancer Patients of Bisphosphonate-Related Osteonecrosis of the Jaw
Authors: Vahtsevanos Konstantinos , Kyrgidis Athanassios , Verrou Evgenia , Katodritou Eirini , Triaridis Stefanos , Andreadis Charalampos G. , Boukovinas Ioannis , Koloutsos Georgios E. , Teleioudis Zisis , Kitikidou Kyriaki , Paraskevopoulos Panagiotis , Zervas Konstantinos , Antoniades Konstantinos 
Published: October 2009

Purpose The reported incidence of osteonecrosis of the jaw (ONJ) ranges from 0.94% to 18.6%. This cohort study aimed to calculate the incidence of and identify the risk factors for ONJ in patients with cancer treated with intravenous zoledronate, ibandronate, and pamidronate. Patients and Methods Data analyzed included age, sex, smoking status, underlying disease, medical and dental history, bisphosphonates (BP) type, and doses administered. Relative risks, crude and adjusted odds ratios (aORs), and cumulative hazard ratios for ONJ development were calculated. Results We included 1,621 patients who received 29,006 intravenous doses of BP, given monthly. Crude ONJ incidence was 8.5%, 3.1%, and 4.9% in patients with multiple myeloma, breast cancer, and prostate cancer, respectively. Patients with breast cancer demonstrated a reduced risk for ONJ development, which turned out to be nonsignificant after adjustment for other variables. Multivariate analysis demonstrated that use of dentures (aOR = 2.02; 95% CI, 1.03 to 3.96), history of dental extraction (aOR = 32.97; 95% CI, 18.02 to 60.31), having ever received zoledronate (aOR = 28.09; 95% CI, 5.74 to 137.43), and each zoledronate dose (aOR = 2.02; 95% CI, 1.15 to 3.56) were associated with increased risk for ONJ development. Smoking, periodontitis, and root canal treatment did not increase risk for ONJ in patients receiving BP. Conclusion The conclusions of this study validated dental extractions and use of dentures as risk factors for ONJ development. Ibandronate and pamidronate at the dosages and frequency used in this study seem to exhibit a safer drug profile concerning ONJ complication; however, randomized controlled trials are needed to validate these results. Before initiation of a bisphosphonate, patients should have a comprehensive dental examination. Patients with a challenging dental situation should have dental care attended to before initiation of these drugs.
Racial and Ethnic Disparities in the Use of Postmastectomy Breast Reconstruction: Results From a Population- Based Study
Authors: Alderman Amy K. , Hawley Sarah T. , Janz Nancy K. , Mujahid Mahasin S. , Morrow Monica , Hamilton Ann S. , Graff John J. , Katz Steven J. 
Published: October 2009

Purpose There is concern that minority women have limited access to breast reconstruction. We described patterns of use, experiences with clinicians, and patients' satisfaction with treatment decisions for women of different race/ethnicities. Methods A total of 3,252 patients with breast cancer from Los Angeles and Detroit Surveillance, Epidemiology, and End Results registries were surveyed near the time of diagnosis (n = 2,260, response rate 72.2%). The primary outcomes were receipt of reconstruction, access to information about reconstruction, and decisional satisfaction. The primary independent variable was race/ethnicity (white, African American [AA], highly acculturated Latina [Latina-high], and less acculturated Latina [Latina-low]). Control variables included other sociodemographic and clinical factors. χ2 and multivariate logistic regression were used for the analyses. Results Receipt of reconstruction varied significantly by patient race/ethnicity—40.9% of whites, 33.5% of AAs, 41.2% of Latina-high, and only 13.5% of Latina-low (P < .001)—and persisted when we controlled for demographic and clinical factors. Minority women were significantly less likely than whites to see a plastic surgeon before initial surgery and were more likely to desire more information about reconstruction (17.0% of whites v 27.0% of AAs, 30.0% of Latina-high, and 55.9% of Latina-low; P < .001). Decisional satisfaction was lowest among minority women without reconstruction (P < .001). Conclusion Minority women, particularly less acculturated Latinas, had low receipt of breast reconstruction, which may be related to limited information about the procedure and less access to plastic surgeons. Greater desire for information and lower satisfaction with surgical decisions among these patients motivate greater attention to treatment support for these patients.
Quality of Life of Patients With Endometrial Cancer Undergoing Laparoscopic International Federation of Gynecology and Obstetrics Staging Compared With Laparotomy: A Gynecologic Oncology Group Study
Authors: Kornblith Alice B. , Huang Helen Q. , Walker Joan L. , Spirtos Nick M. , Rotmensch Jacob , Cella David 
Published: October 2009

Purpose The study's objective was to compare the quality of life (QoL) of patients with endometrial cancer undergoing surgical staging via laparoscopy versus laparotomy. Patients and Methods The first 802 eligible patients (laparoscopy, n = 535; laparotomy, n = 267) participated in the QoL study in a Gynecologic Oncology Group (GOG) randomized trial of laparoscopy versus laparotomy (GOG 2222). Patients completed QoL assessments at baseline; at 1, 3, and 6 weeks; and at 6 months postsurgery. Results In an intent-to-treat analysis, laparoscopy patients reported significantly higher Functional Assessment of Cancer Therapy–General (FACT-G) scores (P = .001), better physical functioning (P = .006), better body image (BI; P < .001), less pain (P < .001) and its interference with QoL (P < .001), and an earlier resumption of normal activities (P = .003) and return to work (P = .04) over the 6-week postsurgery period, as compared with laparotomy patients. However, the differences in BI and return to work between groups were modest, and the adjusted FACT-G scores did not meet the minimally important difference (MID) between the two surgical arms over 6 weeks. By 6 months, except for better BI in laparoscopy patients (P < .001), the difference in QoL between the two surgical techniques was not statistically significant. Conclusion Although the FACT-G did not show a MID between the two surgical groups, and only modest differences in return to work and BI were found between the two groups, statistically significantly better QoL across many parameters in the laparoscopy arm at 6 weeks provides modest support for the QoL advantage of using laparoscopy to stage patients with early endometrial cancer.
Underweight and Breast Cancer Recurrence and Death: A Report From the Korean Breast Cancer Society
Authors: Moon Hyeong-Gon , Han Wonshik , Noh Dong-Young 
Published: October 2009

Purpose The association between body mass index and breast cancer outcome is controversial. Furthermore, the impact of underweight on breast cancer recurrence and death has not been adequately addressed. Patients and Methods We investigated this issue using a large nationwide database of 24,698 Korean breast cancer patients. The association between body weight status and breast cancer recurrence was further explored using a single-institution database containing information on 4,345 patients. Results The results from the nationwide database showed significantly lower overall survival (OS) and breast cancer-specific survival (BCSS) in underweight patients compared with survival in patients of normal weight after adjusting for known prognostic factors such as age, tumor size, lymph node metastasis, hormone receptor status, histologic grade, and lymphovascular invasion (hazard ratio [HR], 1.48; 95% CI, 1.15 to 1.90 for OS; HR, 1.49; 95% CI, 1.15 to 1.93 for BCSS), which were not observed in obese patients. In an analysis of recurrence data from the single institution, underweight women had a significantly higher risk of both distant metastasis and local recurrence of breast cancer (HR, 1.93; 95% CI, 1.04 to 3.58 and HR, 5.13; 95% CI, 2.66 to 9.90, respectively). Conclusion Our study suggests that underweight should be considered to be a high risk factor for death and recurrence after breast cancer surgery, especially in Asian breast cancer patients.
Timed Sequential Treatment With Cyclophosphamide, Doxorubicin, and an Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor–Secreting Breast Tumor Vaccine: A Chemotherapy Dose-Ranging Factorial Study of Safety and Immune Activation
Authors: Emens Leisha A. , Asquith Justin M. , Leatherman James M. , Kobrin Barry J. , Petrik Silvia , Laiko Marina , Levi Joy , Daphtary Maithili M. , Biedrzycki Barbara , Wolff Antonio C. , Stearns Vered , Disis Mary L. , Ye Xiaobu , Piantadosi Steven , Fetting John H. , Davidson Nancy E. , Jaffee Elizabeth M. 
Published: October 2009

Purpose Granulocyte-macrophage colony-stimulating factor (GM-CSF) –secreting tumor vaccines have demonstrated bioactivity but may be limited by disease burdens and immune tolerance. We tested the hypothesis that cyclophosphamide (CY) and doxorubicin (DOX) can enhance vaccine-induced immunity in patients with breast cancer. Patients and Methods We conducted a 3 × 3 factorial (response surface) dose-ranging study of CY, DOX, and an HER2-positive, allogeneic, GM-CSF–secreting tumor vaccine in 28 patients with metastatic breast cancer. Patients received three monthly immunizations, with a boost 6 to 8 months from study entry. Primary objectives included safety and determination of the chemotherapy doses that maximize HER2-specific immunity. Results Twenty-eight patients received at least one immunization, and 16 patients received four immunizations. No dose-limiting toxicities were observed. HER2-specific delayed-type hypersensitivity developed in most patients who received vaccine alone or with 200 mg/m2 CY. HER2-specific antibody responses were enhanced by 200 mg/m2 CY and 35 mg/m2 DOX, but higher CY doses suppressed immunity. Analyses revealed that CY at 200 mg/m2 and DOX at 35 mg/m2 is the combination that produced the highest antibody responses. Conclusion First, immunotherapy with an allogeneic, HER2-positive, GM-CSF–secreting breast tumor vaccine alone or with CY and DOX is safe and induces HER2-specific immunity in patients with metastatic breast cancer. Second, the immunomodulatory activity of low-dose CY has a narrow therapeutic window, with an optimal dose not exceeding 200 mg/m2. Third, factorial designs provide an opportunity to identify the most active combination of interacting drugs in patients. Further investigation of the impact of chemotherapy on vaccine-induced immunity is warranted.