Outcomes following long-term disease control with immune checkpoint inhibitors in patients with advanced melanoma.

Immune checkpoint inhibitors (ICI) can achieve durable responses in patients with advanced melanoma, and results from clinical trials suggest cure may be possible for a subset of patients. Despite clinical trial data, little is known about the risk, character, and clinical outcome of late recurrences after ICI. This study aimed to explore the disease outcomes and survival in a cohort of patients with long-term responses to ICI.

Comparison of Creatinine, Urea, Ionized Calcium, and Bicarbonate Methods by 2 POC Systems and a Mainframe Chemistry Analyzer.

Background: The i-STAT (iST) and GEM Premier ChemSTAT (ChmST) are point-of-care systems that measure electrolytes, metabolites, acid-base parameters, and hematocrit on blood. We compared results for creatinine, urea (blood urea nitrogen [BUN]), total carbon dioxide (tCo2), and ionized calcium (ion Ca) on blood by the ChmST and iST to Beckman DxC600 (DxC600) results for creatinine and urea on plasma and GEM Premier 5000 (GEM5K) results for ion Ca and tCo2 on blood.

Methods: 107 heparinized blood specimens were analyzed on the ChmST and iST systems, with plasma tested by DxC600 for creatinine and BUN and blood tested by GEM5K for ion Ca and tCo2.

International Society of Oncology Pharmacy Practitioners (ISOPP) position statement: Role of the oncology pharmacy team in cancer care.

The Oncology Pharmacy Team (OPT), consisting of specialty-trained pharmacists and/or pharmacy technicians, is an integral component of the multidisciplinary healthcare team (MHT) involved with all aspects of cancer patient care. The OPT fosters quality patient care, safety, and local regulatory compliance. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on five key areas: 1) oncology pharmacy practice as a pharmacy specialty; 2) contributions to patient care; 3) oncology pharmacy practice management; 4) education and training; and 5) contributions to oncology research and quality initiatives to involve the OPT.

Quality Control Practices for Chemistry and Immunochemistry in a Cohort of 21 Large Academic Medical Centers.

Objectives: In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program.

Methods: We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing.

Effect of beef ingestion by humans on plasma concentrations of creatinine, urea, and cystatin C.

Purpose: The effect of eating meat on serum concentrations of creatinine has varied among previous reports, with some finding no effect and others finding 50-100% increases, which appears related to how the beef is cooked. For other analytes related to kidney function, urea is well known to increase following a protein meal, and the effect of eating meat on cystatin C concentrations has been studied once.

Methods: We had 32 participants eat a measured amount of cooked beef (5-6 or 10-12 oz; 142-170 or 284-340 g) and collected blood for measurements at 1 h before and immediately before eating beef, then at 1, 2, and 4 h after eating the beef.

The analytical change in plasma creatinine that constitutes a biologic/physiologic change.

Purpose: Accurate and precise measurements of creatinine are necessary to evaluate changes in kidney function related to a decreased glomerular filtration rate (GFR). When serial measurements of creatinine are monitored in an individual, it is useful to know what magnitude of an analytical change in creatinine indicates a true physiologic/biologic change in plasma creatinine that might warrant clinical intervention.

Methods: We compared results between three different methods for creatinine using large chemistry analyzers, two based on alkaline picrate (AP1 and AP2), and one based on dry-slide enzymatic conversion (ENZ).

Docetaxel and nab-paclitaxel are safe alternative options for patients with gynecologic malignancies following hypersensitivity reaction to paclitaxel.

Docetaxel and nab-paclitaxel are safe alternatives to paclitaxel after hypersensitivity reaction occurs. There was no significant difference in overall survival between those that had paclitaxel, docetaxel, and nab-paclitaxel.

Implementation of the Pharmacy Practice Model Initiative within comprehensive cancer centers.

Purpose: The progress made by cancer centers across the United States adopting the goals and measures of the Pharmacy Practice Model Initiative (PPMI) was studied.

Methods: In collaboration with ASHP, the official PPMI hospital self-assessment (HSA) questionnaire and a 10-item supplemental survey specific to oncology pharmacy services were disseminated via e-mail to all 41 National Cancer Institute designated comprehensive cancer centers in the United States.

Results: The HSA results of 26 (63%) of the 41 institutions surveyed were included in the analysis.

Does applying technology throughout the medication use process improve patient safety with antineoplastics?

Purpose: Medical errors, in particular medication errors, continue to be a troublesome factor in the delivery of safe and effective patient care. Antineoplastic agents represent a group of medications highly susceptible to medication errors due to their complex regimens and narrow therapeutic indices. As the majority of these medication errors are frequently associated with breakdowns in poorly defined systems, developing technologies and evolving workflows seem to be a logical approach to provide added safeguards against medication errors.

Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors.

Zinc-finger nucleases (ZFNs) have become a valuable tool for targeted genome engineering. Based on the enzyme's ability to create a site-specific DNA double-strand break, ZFNs promote genome editing by activating the cellular DNA damage response, including homology-directed repair (HDR) and nonhomologous end-joining. The goal of this study was (i) to demonstrate the versatility of combining the ZFN technology with a vector platform based on adeno-associated virus (AAV), and (ii) to assess the toxicity evoked by this platform.

MicroRNA-221 regulates FAS-induced fulminant liver failure.

Unlabelled: Death receptor-mediated apoptosis of hepatocytes contributes to hepatitis and fulminant liver failure. MicroRNAs (miRNAs), 19-25 nucleotide-long noncoding RNAs, have been implicated in the posttranscriptional regulation of the various apoptotic pathways. Here we report that global loss of miRNAs in hepatic cells leads to increased cell death in a model of FAS/CD95 receptor-induced apoptosis.

Zinc-finger nuclease based genome surgery: it's all about specificity.

Therapeutic genome engineering is a hallmark of gene therapy but only recent technological advances have permitted the modification of complex genomes in a targeted fashion. Zinc-finger nucleases (ZFNs) have developed into a major playmaker in the genome engineering field and have been employed to trigger the targeted editing of genomes at over 50 gene loci in 11 model organisms, including fruitfly, zebrafish and rat, with allelic frequencies reaching the double digit percentage range. Moreover, ZFN-mediated genome surgery in primary human cells has become a reality and two phase I clinical trials aiming at knocking out the CCR5 receptor in T cells isolated from HIV patients to protect these cells from infection with the virus have been initiated.

alpha(1A)- and alpha(1B)-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse.

Tricyclic antidepressant (TCA) drugs are used for the treatment of chronic depression, obsessive-compulsive disorder (OCD), and anxiety-related disorders. Chronic use of TCA drugs increases the expression of alpha(1)-adrenergic receptors (alpha(1)-ARs). Yet, it is unclear whether increased alpha(1)-AR expression contributes to the antidepressant effects of these drugs or if this effect is unrelated to their therapeutic benefit.

Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity.

Precise manipulations of complex genomes by zinc-finger nucleases (ZFNs) depend on site-specific DNA cleavage, which requires two ZFN subunits to bind to two target half-sites separated by a spacer of 6 base pairs (bp). ZFN subunits consist of a specific DNA-binding domain and a nonspecific cleavage domain, connected by a short inter-domain linker. In this study, we conducted a systematic analysis of 11 candidate-based linkers using episomal and chromosomal targets in two human cell lines.

De novo biosynthesis of juvenile hormone III and I by the accessory glands of the male mosquito.

The role of the male accessory glands (MAG) in reproduction was investigated in the mosquito Aedes aegypti. MAG incubated with [14C]acetate synthesized radioactively labeled JH III, JH III bisepoxide and methyl farnesoate. MAG incubated with L-[methyl-3H]methionine synthesized [3H]JH III and a molecule that chromatographed on HPLC with JH I.

Sulfide sensitivity in fishes of the Indian River lagoon, Florida.

Lagoon fishes, in netted holding cages, were placed in an impounded salt marsh and submitted to a gradient of sulfide-rich artesian well water. Near the well head, all specimens of 13 species died within 5-45 min, while all individuals of 5 species survived. More distant from the well, survival time increased sufficiently to rank species in approximate order of sensitivity to sulfide.

Sugar-deprivation following a blood meal does not reduce yolk formation and fertility in Culex quinquefasciatus.

Adult Culex quinquefasciatus, maintained from emergence on sugar, were fed blood and then fed either sugar (control) or water (starving) for 7 days. Analysis of ovaries and egg rafts for protein, lipids and glycogen showed that only glycogen levels were diminished by starvation. Eggs from both control and starving females, however, were equally viable.

Nectar-feeding habits of Aedes taeniorhynchus.

Aedes taeniorhynchus were collected on the wing at several times during the day and night, in Indian River and Brevard County, Florida. Nonblooded females were individually analyzed for fructose and glycogen. Fructose content of mosquitoes collected early in the morning and held without food during the day diminished to approximately the same level as in mosquitoes collected late in the afternoon.

Correlation between wing length and protein content of mosquitoes.

Wing length and protein content were compared in individual specimens of male and nonbloodfed, nongravid female mosquitoes. The following groups were tested: field-collected and colonized Aedes aegypti, field-collected Culex nigripalpus and Aedes vexans, and colonized Culex quinquefasciatus and Psorophora columbiae. The correlation coefficient varied from 0.