bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxic epidermal necrolysis following treatment of pseudotumour cerebri: a case report
Authors: El Ghonemi Mohamed , Omar Hesham R , Rashad Rania , Kolla Jaya , Mangar Devanand , Camporesi Enrico 
Published: December 2009

Abstract
Toxic Epidermal Necrolysis and Steven-Johnson syndrome are entities on a spectrum of cutaneous reactions that usually occur as an idiosyncratic reaction to certain drugs. The distinction between TEN and SJS is based on the percentage of skin involved with SJS being less than 10% and TEN being more than 30%. They exhibit severe skin blistering and sloughing with mucosal involvement and can be fatal in many cases. Discontinuation of the offending agent is mandatory together with reduction of skin manipulation and avoiding infection. Plasmapharesis, intravenous immunoglobulins and immunosuppressants have been used with conflicting results. In this manuscript we are describing a 22 year old female patient from Egypt who presented with severe skin sloughing with mucosal involvement following carbamazepine therapy. The incriminated drug was discontinued and urgent life saving therapy in the form of broad spectrum antibiotic, immunosuppression with cyclophosphamide, Intensive Care Unit admission and nursing care was started followed by dramatic response. The clinical presentation, pathogenesis and modalities of treatment will be described in details.
The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study
Authors: Comstedt Pål , Storgaard Merete , Lassen Annmarie T 
Published: December 2009

Abstract

Background
Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown.

Methods
We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality.

Results
A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p < 0.001, relative risk (RR) 2.2 (95% confidence interval (CI) 1.6-3.1), and they had a 6.9 times higher 28-day mortality than non-SIRS patients with 15/154 SIRS patients versus 3/211 non-SIRS patients: p = 0.001, RR 6.9 (95% CI 2.0-23.3). Most of the deaths among patients with SIRS occurred among patients with malignant conditions. Septic shock developed in 4/154 (3%) of the patients with SIRS, whereas this occurred in only one of the 211 patients (0.5%) without SIRS on arrival: p = 0.08, RR 5.5 (95% CI 0.6-48.6).

Conclusion
We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.
Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel in HER2-Positive Metastatic Breast Cancer
Authors: Wardley Andrew M. , Pivot Xavier , Morales-Vasquez Flavia , Zetina Luis M. , de Fátima Dias Gaui Maria , Reyes Douglas Otero , Jassem Jacek , Barton Claire , Button Peter , Hersberger Veronica , Torres Antonio Antón 
Published: December 2009

Purpose To evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. Patients and Methods Patients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2 in HTX arm, 100 mg/m2 in HT arm, every 3 weeks) with or without X (950 mg/m2 twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR). Results In 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm. Conclusion HTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.
Role of Axillary Clearance After a Tumor-Positive Sentinel Node in the Administration of Adjuvant Therapy in Early Breast Cancer
Authors: Straver Marieke E. , Meijnen Philip , van Tienhoven Geertjan , van de Velde Cornelis J.H. , Mansel Robert E. , Bogaerts Jan , Demonty Gaston , Duez Nicole , Cataliotti Luigi , Klinkenbijl Jean , Westenberg Helen A. , van der Mijle Huub , Hurkmans Coen , Rutgers Emiel J.T. 
Published: December 2009

Purpose The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase III study compares axillary lymph node dissection (ALND) and axillary radiation therapy (ART) in early breast cancer patients with tumor-positive sentinel nodes. In the ART arm, the extent of nodal involvement remains unknown, which could have implications on the administration of adjuvant therapy. In this preliminary analysis, we studied the influence of random assignment to ALND or ART on the choice for adjuvant treatment. Patients and Methods In the first 2,000 patients enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic therapy. Multivariate analysis was used to assess variables affecting the administration of adjuvant chemotherapy. Adjuvant therapy was applied according to institutional guidelines. Results Of 2,000 patients, 566 patients had a positive sentinel node and were treated per random assignment. There was no significant difference in the administration of adjuvant systemic therapy. In the ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients, respectively, received chemotherapy. Endocrine therapy was administered in 78% (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the patients in the ART arm. Treatment arm was not a significant factor in the decision, and no interactions between treatment arm and other factors were observed. Multivariate analysis showed that age, tumor grade, multifocality, and size of the sentinel node metastasis significantly affected the administration of chemotherapy. Within the ALND arm, the extent of nodal involvement remained not significant in a sensitivity multivariate analysis. Conclusion Absence of knowledge regarding the extent of nodal involvement in the ART arm appears to have no major impact on the administration of adjuvant therapy.
Single Nucleotide Polymorphism in the Mutational Hotspot ofWT1Predicts a Favorable Outcome in Patients With Cytogenetically Normal Acute Myeloid Leukemia
Authors: Damm Frederik , Heuser Michael , Morgan Michael , Yun Haiyang , Großhennig Anika , Göhring Gudrun , Schlegelberger Brigitte , Döhner Konstanze , Ottmann Oliver , Lübbert Michael , Heit Wolfgang , Kanz Lothar , Schlimok Günter , Raghavachar Aruna , Fiedler Walter , Kirchner Hartmut , Döhner Hartmut , Heil Gerhard , Ganser Arnold , Krauter Jürgen 
Published: December 2009

PurposeWe assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.Patients and MethodsWT1 exons 7 and 9 from 249 CN-AML patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1 expression was quantified.ResultsThe minor allele of SNP rs16754 (WT1AG/GG) was found in 25.7% of CN-AML patients' blasts and germline DNA and in 36% of healthy volunteers. Patient characteristics, frequencies of mutations, or WT1 expression levels were similarly distributed between patients homozygous for the major allele compared with patients heterozygous or homozygous for the minor allele. SNP rs16754 status was an independent predictor of relapse-free survival (RFS; hazard ratio [HR], 0.49; 95% CI, 0.3 to 0.81; P = .005) and overall survival (OS; HR, 0.44; 95% CI, 0.27 to 0.74; P = .002) in multivariate analysis. The favorable effect of SNP rs16754 was stronger in NPM1/FLT3-ITD (internal tandem duplication of the FLT3 gene) high-risk patients compared with NPM1/FLT3-ITD low-risk patients. Favorable prognosis could not be identified by any other known low-risk marker in half the patients with at least one minor allele (13% of all patients). No difference for complete remission rate, RFS, or OS was found between patients with or without acquired WT1 mutations.ConclusionWT1 SNP rs16754 may be a novel independent favorable-risk marker in CN-AML patients that might improve risk and treatment stratification.
Randomized Phase III Trial of Platinum-Doublet Chemotherapy Followed by Gefitinib Compared With Continued Platinum-Doublet Chemotherapy in Japanese Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Thoracic Oncology Group Trial (WJTOG0203)
Authors: Takeda Koji , Hida Toyoaki , Sato Tosiya , Ando Masahiko , Seto Takashi , Satouchi Miyako , Ichinose Yukito , Katakami Nobuyuki , Yamamoto Nobuyuki , Kudoh Shinzoh , Sasaki Jiichiro , Matsui Kaoru , Takayama Koichi , Kashii Tatsuhiko , Iwamoto Yasuo , Sawa Toshiyuki , Okamoto Isamu , Kurata Takayasu , Nakagawa Kazuhiko , Fukuoka Masahiro 
Published: December 2009

PurposeGefitinib is a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase. We conducted a phase III trial to evaluate whether gefitinib improves survival as sequential therapy after platinum-doublet chemotherapy in patients with advanced non–small-cell lung cancer (NSCLC).Patients and MethodsChemotherapy-naïve patients with advanced stage (IIIB/IV) NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and adequate organ function were randomly assigned to either platinum-doublet chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three cycles followed by gefitinib 250 mg orally once daily, until disease progression (arm B). Patients were stratified by disease stage, sex, histology, and chemotherapy regimens. The primary end point was overall survival; secondary end points included progression-free survival, tumor response, safety, and quality of life.ResultsBetween March 2003 and May 2005, 604 patients were randomly assigned. There was a statistically significant improvement in progression-free survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P < .001); however, overall survival results did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of overall survival by histologic group, patients in arm B with adenocarcinoma did significantly better than patients in arm A with adenocarcinoma (n = 467; HR, 0.79; 95% CI, 0.65 to 0.98; P = .03).ConclusionThis trial failed to meet the primary end point of OS in patients with NSCLC. The exploratory subset analyses demonstrate a possible survival prolongation for sequential therapy of gefitinib, especially for patients with adenocarcinoma.
Acupuncture Versus Venlafaxine for the Management of Vasomotor Symptoms in Patients With Hormone Receptor–Positive Breast Cancer: A Randomized Controlled Trial
Authors: Walker Eleanor M. , Rodriguez Alba I. , Kohn Beth , Ball Ronald M. , Pegg Jan , Pocock Jeffrey R. , Nunez Ramon , Peterson Ed , Jakary Susan , Levine Robert A. 
Published: December 2009

Purpose Vasomotor symptoms are common adverse effects of antiestrogen hormone treatment in conventional breast cancer care. Hormone replacement therapy is contraindicated in patients with breast cancer. Venlafaxine (Effexor), the therapy of choice for these symptoms, has numerous adverse effects. Recent studies suggest acupuncture may be effective in reducing vasomotor symptoms in menopausal women. This randomized controlled trial tested whether acupuncture reduces vasomotor symptoms and produces fewer adverse effects than venlafaxine. Patients and Methods Fifty patients were randomly assigned to receive 12 weeks of acupuncture (n = 25) or venlafaxine (n = 25) treatment. Health outcomes were measured for up to 1 year post-treatment. Results Both groups exhibited significant decreases in hot flashes, depressive symptoms, and other quality-of-life symptoms, including significant improvements in mental health from pre- to post-treatment. These changes were similar in both groups, indicating that acupuncture was as effective as venlafaxine. By 2 weeks post-treatment, the venlafaxine group experienced significant increases in hot flashes, whereas hot flashes in the acupuncture group remained at low levels. The venlafaxine group experienced 18 incidences of adverse effects (eg, nausea, dry mouth, dizziness, anxiety), whereas the acupuncture group experienced no negative adverse effects. Acupuncture had the additional benefit of increased sex drive in some women, and most reported an improvement in their energy, clarity of thought, and sense of well-being. Conclusion Acupuncture appears to be equivalent to drug therapy in these patients. It is a safe, effective and durable treatment for vasomotor symptoms secondary to long-term antiestrogen hormone use in patients with breast cancer.
Genotype-Driven Phase I Study of Irinotecan Administered in Combination With Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer
Authors: Toffoli Giuseppe , Cecchin Erika , Gasparini Giampiero , D'Andrea Mario , Azzarello Giuseppe , Basso Umberto , Mini Enrico , Pessa Sergio , De Mattia Elena , Lo Re Giovanni , Buonadonna Angela , Nobili Stefania , De Paoli Paolo , Innocenti Federico 
Published: December 2009

Purpose We aimed to identify the maximum-tolerated dose (MTD) of irinotecan in patients with cancer with UGT1A1*1/*1 and *1/*28 genotypes. We hypothesize that the patients without the *28/*28 genotype tolerate higher doses of irinotecan. Patients and Methods Patients undergoing first-line treatment for metastatic colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype and excluded from the study. Fifty-nine white patients with either the *1/*1 or the *1/*28 genotype were eligible for dose escalation of irinotecan. The starting dose of biweekly irinotecan was 215 mg/m2 for both genotype groups, whereas the dose of infusional fluorouracil was fixed. Pharmacokinetic data of irinotecan and metabolites were also obtained. Results The dose of irinotecan was escalated to 370 mg/m2 in patients with the *1/*28 genotype and to 420 mg/m2 in those with the *1/*1 genotype. Dose-limiting toxicities (DLTs) were observed in two of four of *1/*28 patients at 370 mg/m2 and in two of three of *1/*1 patients at 420 mg/m2. No DLTs were observed in 10 *1/*28 patients at 310 mg/m2 and in 10 *1/*1 patients at 370 mg/m2; hence these dose levels were the MTD for each genotype group. The most common grade 3 to 4 toxicities were neutropenia and diarrhea. The pharmacokinetics of irinotecan and SN-38 exhibit linear kinetics. Conclusion The recommended dose of 180 mg/m2 for irinotecan in FOLFIRI is considerably lower than the dose that can be tolerated when patients with the UGT1A1*28/*28 genotype are excluded. Prospective genotype-driven studies should test the efficacy of higher irinotecan doses in the FOLFIRI schedule.
Adverse Events Among the Elderly Receiving Chemotherapy for Advanced Non–Small-Cell Lung Cancer
Authors: Chrischilles Elizabeth A. , Pendergast Jane F. , Kahn Katherine L. , Wallace Robert B. , Moga Daniela C. , Harrington David P. , Kiefe Catarina I. , Weeks Jane C. , West Dee W. , Zafar S. Yousuf , Fletcher Robert H. 
Published: December 2009

Purpose To describe chemotherapy use and adverse events (AEs) for advanced-stage, non–small-cell lung cancer (NSCLC) in community practice, including descriptions according to variation by age. Methods We interviewed patients with newly diagnosed, stages IIIB and IV NSCLC in the population-based cohort studied by the Cancer Care Outcomes Research and Surveillance Consortium, and we abstracted the patient medical records. AEs were medical events occurring during chemotherapy. Using logistic regression, we assessed the association between age and chemotherapy; with Poisson regression, we estimated event rate ratios and adjusted the analysis for age, sex, ethnicity, radiation therapy, stage, histology, and presence and grade of 27 comorbidities. Results Of 1,371 patients, 58% (95% CI, 55% to 61%) received chemotherapy and 35% (95% CI, 32% to 38%) had AEs. After adjustment, 72% (95% CI, 65% to 79%) of those younger than 55 years and 47% (95% CI, 42% to 52%) of those age 75 years and older received chemotherapy. Platinum-based therapies were less common in the older-age groups. Pretreatment medical event rates were 18.6% for patients younger than 55 years and were only 9.2% for those age 75 years and older (adjusted rate ratio, 0.49; 95% CI, 0.26 to 0.91). In contrast, older adults were more likely to have AEs during chemotherapy. The adjusted rate ratios compared with age younger than 55 years were 1.70 for 65- to 74-year-olds (95% CI, 1.19 to 2.43) and 1.34 for those age 75 years and older (95% CI, 0.90 to 2.00). Conclusion Older patients who received chemotherapy had fewer pretherapy events than younger patients and were less likely to receive platinum-based regimens. Nevertheless, older patients had more adverse events during chemotherapy, independent of comorbidity. Potential implicit trade-offs between symptom management and treatment toxicity should be made explicit and additionally studied.
HER2,TOP2A, and TIMP-1 and Responsiveness to Adjuvant Anthracycline-Containing Chemotherapy in High-Risk Breast Cancer Patients
Authors: Ejlertsen Bent , Jensen Maj-Britt , Nielsen Kirsten V. , Balslev Eva , Rasmussen Birgitte B. , Willemoe Gro L. , Hertel Pernille B. , Knoop Ann S. , Mouridsen Henning T. , Brünner Nils 
Published: December 2009

PurposeTo evaluate whether the combination of HER2 with TIMP-1 (HT) or TOP2A with TIMP-1 (2T) more accurately identifies patients who benefit from cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) than these markers do when analyzed individually.Patients and MethodsThe Danish Breast Cancer Cooperative Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2-negative and TIMP-1 immunoreactive tumors were classified as HT nonresponsive and otherwise HT responsive. Similarly, the 2T panel was constructed by combining TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity were classified as 2T-nonresponsive and otherwise 2T-responsive.ResultsIn total, 623 tumors were available for analysis, of which 154 lacked TIMP-1 immunoreactivity, 188 were HER2 positive, and 139 had a TOP2A aberration. HT status was a statistically significant predictor of benefit from CEF compared with CMF (Pinteraction= .036 for invasive disease–free survival [IDFS] and .047 for overall survival [OS]). The 269 (43%) patients with a 2T-responsive profile had a significant reduction in IDFS events (adjusted hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P < .001) and OS events (adjusted hazard ratio, 0.54; 95% CI, 0.38 to 0.77; P < .001). 2T status was a highly significant predictor of benefit from CEF compared with CMF (Pinteraction< .0001 for IDFS and .004 for OS).ConclusionThe 2T profile is a more accurate predictor of incremental benefit from anthracycline-containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines.
Molecular Predictors of Outcome With Gefitinib and Docetaxel in Previously Treated Non–Small-Cell Lung Cancer: Data From the Randomized Phase III INTEREST Trial
Authors: Douillard Jean-Yves , Shepherd Frances A. , Hirsh Vera , Mok Tony , Socinski Mark A. , Gervais Radj , Liao Mei-Lin , Bischoff Helge , Reck Martin , Sellers Mark V. , Watkins Claire L. , Speake Georgina , Armour Alison A. , Kim Edward S. 
Published: December 2009

Purpose In the phase III INTEREST trial, 1,466 pretreated patients with advanced non–small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. Methods Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations. Results For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation–positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel. Conclusion These biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation–positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.