Safety Analyses of the Phase 3 VISION Trial of [Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer.

Background And Objective: [Lu]Lu-PSMA-617 (Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of Lu-PSMA-617 and the impact of longer observation time for patients receiving Lu-PSMA-617 plus SoC.

Methods: VISION was an international, open-label study.

A VISION Substudy of Reader Agreement on Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for Lu-PSMA-617 Radioligand Therapy.

[ Ga]Ga-PSMA-11 ( Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [Lu]Lu-PSMA-617 (Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study.

Adherence to Hematologic Hold Parameters in Carboplatin and Dose-Dense Paclitaxel Chemotherapy for Ovarian Malignancies: A Survey of NCCN Member Institutions.

Objective: To determine the adherence to hematologic chemotherapy hold parameters for the carboplatin and dose-dense paclitaxel chemotherapy regimen in patients with ovarian, fallopian tube, or primary peritoneal cancers.

Methods: This is a quality assessment survey study. All 26 NCCN Member Institutions were contacted electronically.

Operational challenges and solutions with implementation of an adaptive seamless phase 2/3 study.

A wide variety of operational issues were encountered with the planning and implementation of an adaptive, dose-finding, seamless phase 2/3 trial for a diabetes therapeutic. Compared with a conventional design, significant upfront planning was required, as well as earlier, more integrated cross-functional coordination. The existing infrastructure necessitated greater flexibility to meet the needs of the adaptive design.

Helium pneumoperitoneum ameliorates hypercarbia and acidosis associated with carbon dioxide insufflation during laparoscopic gastric bypass in pigs.

Background: In the morbidly obese patient undergoing laparoscopic gastric bypass (LGBP), insufflation with carbon dioxide to 20 mmHg for prolonged periods may induce significant hypercarbia and acidosis with attendant sequelae. We hypothesize that the use of helium as an insufflating agent results in less hypercarbia and acidosis.

Methods: The study was performed between May and November 2002.

Acute lower gastroenteric bleeding retrospective analysis (the ALGEBRA study): an analysis of the triage, management and outcomes of patients with acute lower gastrointestinal bleeding.

Many algorithms have been developed for patients with acute lower gastrointestinal hemorrhage (ALGIH). Their clinical usefulness is not readily apparent. It is important first to observe patterns in admission, triage, and management to formulate hypotheses as to how outcomes might be affected.

Bare bones laparoscopy: a randomized prospective trial of cost savings in laparoscopic cholecystectomy.

Objective: Rising costs and lowered reimbursements make value essential if laparoscopic cholecystectomy (LC) is to be offered to patients without condemning providers to financial loss. We hypothesize that our protocol increases this value. Once practiced, operative time, complications, and patient satisfaction compare with those of the typical method.

PCR-based ordered genomic libraries: a new approach to drug target identification for Streptococcus pneumoniae.

Described here are the development and validation of a novel approach to identify genes encoding drug targets in Streptococcus pneumoniae. The method relies on the use of an ordered genomic library composed of PCR amplicons that were generated under error-prone conditions so as to introduce random mutations into the DNA. Since some of the mutations occur in drug target-encoding genes and subsequently affect the binding of the drug to its respective cellular target, amplicons containing drug targets can be identified as those producing drug-resistant colonies when transformed into S.

In vitro antimicrobial activity of the thiazolyl peptide antibiotic MDL 62,879 (GE2270 A).

Compound MDL 62,879 (GE2270 A) is a thiazolyl peptide antibiotic that appears to inhibit aminoacyl-tRNA binding to elongation factor Tu. In the present study, it was shown that MDL 62,879 broth microdilution MIC values were generally 2-4 doubling dilutions lower in the presence of 0.02% bovine serum albumin.

Comparison of biological and chemical assays for the quantitation of rifapentine in human plasma.

The purpose of this study was to establish the correlation between biological and chemical assays for the quantification of rifapentine in human plasma. The bioassay was found to overestimate antibiotic plasma concentration when compared to the high-performance liquid chromatography (HPLC) assay for rifapentine (r = 0.9538, n = 220).

In vitro activity of the semisynthetic glycopeptide amide MDL 63,246.

The in vitro activity of the semisynthetic glycopeptide amide MDL 63,246 against 293 U.S. clinical isolates of gram-positive cocci was determined by the broth microdilution method.

Comparison of agar dilution, tube dilution, and broth microdilution susceptibility tests for determination of ramoplanin MICs.

Standard broth microdilution (with and without bovine serum albumin [BSA] supplementation), tube dilution, and agar dilution susceptibility tests were compared for determining ramoplanin MICs. With a data base of 246 clinical isolates of gram-positive bacteria from 33 U.S.

Bioassay quantitation of ramoplanin in human and in nonprimate sera.

This study developed and validated a bioassay for ramoplanin in human, dog, rabbit, and rat sera. Mean analyte recoveries and coefficients of variation for duplicate assays with each serum using coded and spiked (30-720 ng/ml) samples ranged from 93.5% to 106.

Evaluation of the teicoplanin broth microdilution and disk diffusion susceptibility tests and recommended interpretive criteria.

Comparative teicoplanin in vitro susceptibility data were generated for 1201 Gram-positive US clinical trial isolates using standardized broth microdilution and disk diffusion techniques. Based on the results of this study, the following interpretive criteria for teicoplanin are recommended: for MIC tests, less than or equal to 8 micrograms/ml = susceptible, 16 micrograms/ml = moderately susceptible, and greater than or equal to 32 micrograms/ml = resistant; and for disk (30 micrograms) tests, greater than or equal to 14 mm = susceptible, 11-13 mm = intermediate, and less than or equal to 10 mm = resistant.

Pharmacokinetics of teicoplanin upon multiple-dose intravenous administration of 3, 12, and 30 milligrams per kilogram of body weight to healthy male volunteers.

Teicoplanin pharmacokinetics were evaluated after multiple-dose intravenous administration to healthy male volunteers by using a randomized, double-blind, parallel design. Doses of 3, 12, or 30 mg of teicoplanin per kg of body weight were administered every 24 h for 14 days as 60-min constant-rate intravenous infusions. Blood and urine samples were collected over 21 days and analyzed by a microbiological assay.

Pharmacokinetics and bioavailability of a new formulation of teicoplanin following intravenous and intramuscular administration to humans.

Pharmacokinetics, bioavailability, and local tolerance (at the site of intramuscular administration) of a new formulation of teicoplanin (400 mg/3 mL) were investigated in 24 normal, healthy, male volunteers. A single dose of 6 mg/kg was administered intravenously and intramuscularly using a randomized crossover design. Volunteers and investigator were blinded as to the route of administration; placebo was administered by the other route.

Comparative in vitro activity of teicoplanin and vancomycin against United States teicoplanin clinical trial isolates of gram-positive cocci.

In this study, the in vitro activity of teicoplanin and vancomycin was directly compared against 503 Gram-positive cocci isolated during the U.S. teicoplanin clinical trials.

Bioassay of teicoplanin in serum containing rifampin or a beta-lactam antibiotic.

The purpose of this study was to develop bioassays for the measurement of teicoplanin in serum containing rifampin or a beta-lactam antibiotic. Use of rifampin-resistant Bacillus subtilis as indicator organism or pretreatment of the serum sample with Bacillus cereus penicillinase Type I (nafcillin, ticarcillin, mezlocillin) or Type II (cefazolin, cefuroxime, ceftazidime, ceftriaxone) effectively eliminated assay interference. Validation bioassays performed on two separate days utilizing triplicate coded serum samples containing 0 to 200 micrograms teicoplanin in combination with 40 micrograms/ml rifampin or 200 to 500 micrograms/ml beta-lactam showed no significant differences (p greater than 0.

Comparison of the agar dilution, tube dilution, and broth microdilution susceptibility tests for determination of teicoplanin MICs.

The purpose of this study was to evaluate the National Committee for Clinical Laboratory Standards agar dilution, tube dilution, and broth microdilution susceptibility tests for the measurement of teicoplanin MICs. The three standardized tests gave equivalent (within a twofold dilution) results with 98.8 to 99.