Clinical outcome of patients with and without diabetes mellitus after percutaneous coronary intervention with the resolute zotarolimus-eluting stent: 2-year results from the prospectively pooled analysis of the international global RESOLUTE program

OBJECTIVES The aim of this study was to describe the process to obtain Food and Drug Administration (FDA) approval for the expanded indication for treatment with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Inc., Santa Rosa, California) in patients with coronary artery disease and diabetes. BACKGROUND The R-ZES is the first drug-eluting stent specifically indicated in the United States for percutaneous coronary intervention in patients with diabetes. METHODS We pooled patient-level data for 5,130 patients from the RESOLUTE Global Clinical Program. A performance goal prospectively determined in conjunction with the FDA was established as a rate of target vessel failure at 12 months of 14.5%. In addition to the FDA pre-specified cohort of less complex patients with diabetes (n = 878), we evaluated outcomes of the R-ZES in all 1,535 patients with diabetes compared with all 3,595 patients without diabetes at 2 years. RESULTS The 12-month rate of target vessel failure in the pre-specified diabetic cohort was 7.8% (upper 95% confidence interval: 9.51%), significantly lower than the performance goal of 14.5% (p < 0.001). After 2 years, the cumulative incidence of target lesion failure in patients with noninsulin-treated diabetes was comparable to that of patients without diabetes (8.0% vs. 7.1%). The higher risk insulin-treated population demonstrated a significantly higher target lesion failure rate (13.7%). In the whole population, including complex patients, rates of stent thrombosis were not significantly different between patients with and without diabetes (1.2% vs. 0.8%). CONCLUSIONS The R-ZES is safe and effective in patients with diabetes. Long-term clinical data of patients with noninsulin-treated diabetes are equivalent to patients without diabetes. Patients with insulin-treated diabetes remain a higher risk subset. (The Medtronic RESOLUTE Clinical Trial; NCT00248079; Randomized, Two-arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; The Medtronic RESOLUTE US Clinical Trial (R-US); NCT00726453; RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [R-Int]; NCT00752128; RESOLUTE Japan-The Clinical Evaluation of the MDT-4107 Drug-Eluting Coronary Stent [RJ]; NCT00927940).

Clinical outcomes of the resolute zotarolimus-eluting stent in patients with in-stent restenosis: 2-year results from a pooled analysis

OBJECTIVES This study sought to assess the clinical safety and effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in patients with in-stent restenosis (ISR) from 2 large trials. BACKGROUND ISR treatment is associated with higher rates of subsequent cardiac events compared with treatment of de novo lesions. Although drug-eluting stents (DES) are an option, second-generation DES are largely untested in the treatment of ISR. METHODS A total of 3,489 patients were pooled from the RAC (RESOLUTE All Comers) trial and the RESOLUTE International (RINT) registry. Two-year clinical endpoints included clinically driven target lesion revascularization (TLR), target lesion failure (TLF), cardiac death (CD), target vessel myocardial infarction (TVMI), combined CD or TVMI (CD/TVMI), and Academic Research Consortium definite and probable stent thrombosis (ST). RESULTS Overall, 281 patients (8.1%) received an R-ZES for ISR. Two-year TLR and TLF rates were significantly higher in ISR patients than in non-ISR patients (TLR: 12.7% vs. 4.3%, p = 0.003; TLF: 17.4% vs. 9.4%, p = 0.007); however, the CD/TVMI rate was not (6.9% vs. 6.1%, p = 0.711). Seven ISR patients had ST. Two-year outcomes by ISR stent type were similar: bare-metal stent (BMS)-ISR TLR was 12.5% and TLF was 17.2%; DES-ISR TLR was 13.0% and TLF was 18.8%. CD/TVMI was 7.3% and 7.2% for BMS-ISR and DES-ISR, respectively. CONCLUSIONS Using R-ZES to treat ISR appears equally safe in BMS-ISR and DES-ISR, with CD/TVMI rates comparable to 2-year outcomes in other clinical trials. Although revascularization rates are still higher in ISR lesions, the R-ZES offers an effective alternative for treatment of BMS-ISR and DES-ISR. (Randomized, Two-Arm, Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent [RESOLUTE-AC]; NCT00617084; and RESOLUTE International Registry: Evaluation of the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient Population [RINT]; NCT00752128).

High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up

In progressive immunoglobulin A nephropathy (IgAN), intravenous immunoglobulin (IVIg) treatment has been used to delay disease progression, but the long-term efficacy is largely unknown. We report the clinical outcomes after IVIg therapy in six male patients with progressive IgAN [median glomerular filtration rate (GFR) 31 ml/min per 1.73 m(2)] followed for a median observation period of 8 years. In this single-arm, non-randomized study, IVIg was given monthly at a dose of 2 g/kg body weight for 6 months. The course of renal function was assessed by linear regression analysis of GFR and proteinuria, and was compared to eight patients with IgAN (median GFR 29 ml/min per 1.73 m(2)) without IVIg as a contemporaneous control group. IgAN disease progression was delayed after IVIg therapy on average for 3 years. The mean loss of renal function decreased from -1.05 ml/min per month to -0.15 ml/min per month (P = 0.024) and proteinuria decreased from 2.4 g/l to 1.0 g/l (P = 0.015). The primary end-point (GFR < 10 ml/min or relapse) occurred 5.2 years (median; range 0.4-8.8) after the first IVIg pulse, and after 1.3 years (median; range 0.8-2.4) in the control group (P = 0.043). In Kaplan-Meier analysis, the median renal survival time with IVIg was prolonged by 3.5 years (IVIg 4.7 years versus control 1.2 years; P = 0.006). IVIg pulse therapy may be considered as a treatment option to reduce the loss of renal function and improve proteinuria in patients with progressive IgAN.

Personalized X-Ray Reconstruction of the Proximal Femur via Intensity-Based Non-rigid 2D-3D Registration

This paper presents a new approach for reconstructing a patient-specific shape model and internal relative intensity distribution of the proximal femur from a limited number (e.g., 2) of calibrated C-arm images or X-ray radiographs. Our approach uses independent shape and appearance models that are learned from a set of training data to encode the a priori information about the proximal femur. An intensity-based non-rigid 2D-3D registration algorithm is then proposed to deformably fit the learned models to the input images. The fitting is conducted iteratively by minimizing the dissimilarity between the input images and the associated digitally reconstructed radiographs of the learned models together with regularization terms encoding the strain energy of the forward deformation and the smoothness of the inverse deformation. Comprehensive experiments conducted on images of cadaveric femurs and on clinical datasets demonstrate the efficacy of the present approach.

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group

GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics

PURPOSE To explore whether population-related pharmacogenomics contribute to differences in patient outcomes between clinical trials performed in Japan and the United States, given similar study designs, eligibility criteria, staging, and treatment regimens. METHODS We prospectively designed and conducted three phase III trials (Four-Arm Cooperative Study, LC00-03, and S0003) in advanced-stage, non-small-cell lung cancer, each with a common arm of paclitaxel plus carboplatin. Genomic DNA was collected from patients in LC00-03 and S0003 who received paclitaxel (225 mg/m(2)) and carboplatin (area under the concentration-time curve, 6). Genotypic variants of CYP3A4, CYP3A5, CYP2C8, NR1I2-206, ABCB1, ERCC1, and ERCC2 were analyzed by pyrosequencing or by PCR restriction fragment length polymorphism. Results were assessed by Cox model for survival and by logistic regression for response and toxicity. Results Clinical results were similar in the two Japanese trials, and were significantly different from the US trial, for survival, neutropenia, febrile neutropenia, and anemia. There was a significant difference between Japanese and US patients in genotypic distribution for CYP3A4*1B (P = .01), CYP3A5*3C (P = .03), ERCC1 118 (P < .0001), ERCC2 K751Q (P < .001), and CYP2C8 R139K (P = .01). Genotypic associations were observed between CYP3A4*1B for progression-free survival (hazard ratio [HR], 0.36; 95% CI, 0.14 to 0.94; P = .04) and ERCC2 K751Q for response (HR, 0.33; 95% CI, 0.13 to 0.83; P = .02). For grade 4 neutropenia, the HR for ABCB1 3425C-->T was 1.84 (95% CI, 0.77 to 4.48; P = .19). CONCLUSION Differences in allelic distribution for genes involved in paclitaxel disposition or DNA repair were observed between Japanese and US patients. In an exploratory analysis, genotype-related associations with patient outcomes were observed for CYP3A4*1B and ERCC2 K751Q. This common-arm approach facilitates the prospective study of population-related pharmacogenomics in which ethnic differences in antineoplastic drug disposition are anticipated.

Non-rigid Free-Form 2D-3D Registration Using Statistical Deformation Model

This paper presents a non-rigid free-from 2D-3D registration approach using statistical deformation model (SDM). In our approach the SDM is first constructed from a set of training data using a non-rigid registration algorithm based on b-spline free-form deformation to encode a priori information about the underlying anatomy. A novel intensity-based non-rigid 2D-3D registration algorithm is then presented to iteratively fit the 3D b-spline-based SDM to the 2D X-ray images of an unseen subject, which requires a computationally expensive inversion of the instantiated deformation in each iteration. In this paper, we propose to solve this challenge with a fast B-spline pseudo-inversion algorithm that is implemented on graphics processing unit (GPU). Experiments conducted on C-arm and X-ray images of cadaveric femurs demonstrate the efficacy of the present approach.

Palatal swelling as the first and only manifestation of extranodal follicular non-Hodgkin lymphoma: a case presentation

Non-Hodgkin lymphomas (NHLs) in the head and neck region are malignant lymphoid neoplasms that usually originate from B-lymphocytic cell lines. Primary extranodal manifestations of this hematolymphoid tumor in the oral cavity are rare and involve the maxillary jaw including the palatal soft tissues, the mandible, and gingival tissues in patients between 60 and 70 years of age without sex predilection. This case report of an extra-nodal NHL in the palate of a 75-year-old patient emphasizes the importance of accurate clinical, radiographic, and histologic diagnostic procedures to avoid delayed diagnosis or inappropriate treatment strategies. Chemotherapy, radiotherapy, or a combination of the two with a regular clinical and hemic follow-up is recommended.