Ten years of experience with ruxolitinib since approval for polycythemia vera: A review of clinical efficacy and safety.

The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU.

Real-World Use of Ruxolitinib Cream: Safety Analysis at 1 Year.

Background: Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and nonsegmental vitiligo. A postmarketing study with oral tofacitinib, approved for rheumatoid arthritis, triggered class warnings for JAK inhibitors, including risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. Because ruxolitinib cream is indicated for inflammatory conditions, it is subject to the same warnings as oral JAK inhibitors in the US.

Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials.

Effects of Mouse Kidney Parvovirus on Pharmacokinetics of Chemotherapeutics and the Adenine Model of Chronic Kidney Disease.

Mouse kidney parvovirus (MKPV) causes inclusion body nephropathy in severely immunocompromised mice and renal interstitial inflammation in immunocompetent mice. Here we sought to determine the effects of MKPV on pre-clinical murine models that depend on renal function. To assess the effects of MKPV infection on the pharmacokinetics of 2 renally excreted chemotherapeutic agents, methotrexate and lenalidomide, we measured drug concentrations in the blood and urine of MKPV-infected or uninfected immunodeficient NOD.

Clinical Performance Characteristics of the Swift Normalase Amplicon Panel for Sensitive Recovery of Severe Acute Respiratory Syndrome Coronavirus 2 Genomes.

Amplicon-based sequencing methods are central in characterizing the diversity, transmission, and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but need to be rigorously assessed for clinical utility. Herein, we validated the Swift Biosciences' SARS-CoV-2 Swift Normalase Amplicon Panels using remnant clinical specimens. High-quality genomes meeting our established library and sequence quality criteria were recovered from positive specimens, with 95% limit of detection of 40.

Variants of Concern Are Overrepresented Among Postvaccination Breakthrough Infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Washington State.

Across 20 vaccine breakthrough cases detected at our institution, all 20 (100%) infections were due to variants of concern (VOCs) and had a median Ct of 20.2 (IQR, 17.1-23.

Evaluation of In-cage Filter Paper as a Replacement for Sentinel Mice in the Detection of Murine Pathogens.

Recent studies have evaluated alternatives to the use of live animals in colony health monitoring. Currently, an alternative method that is suitable for all rack types and that has been verified to detect the infectious agents most commonly excluded from mouse colonies is unavailable. We compared the use of filter paper placed on the inside floor of mouse cages to the traditional use of sentinel mice in the detection of several prevalent murine pathogens including mouse hepatitis virus (MHV), murine norovirus (MNV), minute virus of mice (MVM), mouse parvovirus (MPV), Theiler murine encephalomyelitis virus (TMEV), spp.

LEPTOSPIRA, PARVOVIRUS, AND TOXOPLASMA IN THE NORTH AMERICAN RIVER OTTER (LONTRA CANADENSIS) IN NORTH CAROLINA, USA.

The North American river otter (Lontra canadensis) is the largest mustelid in North Carolina, US, and was once extirpated from the central and western portions of the state. Over time and after a successful reintroduction project, otters are now abundant and occur throughout North Carolina. However, there is a concern that diseases may have an impact on the otter population, as well as on other aquatic mammals, either through exposure to emerging diseases, contact with domestic animals such as domestic cats (Felis catus), or less robust condition of individuals through declines in water quality.

Association Between 21-Gene Assay Recurrence Score and Locoregional Recurrence Rates in Patients With Node-Positive Breast Cancer.

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain.

Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone.

Design, Setting, And Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy.

Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307.

Background: Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer.

Effects of Pelleting, Irradiation, and Autoclaving of Rodent Feed on MPV and MNV Infectivity.

Murine norovirus (MNV) and mouse parvovirus (MPV) are among the most common adventitial viruses seen in laboratory mice, and infections arise in barrier facilities despite rigorous biosecurity programs. Some authors have implicated nonsterilized feed as a source of MPV in rodent facilities, but none have conclusively documented viral particles in the feed. In this study, we hypothesized that both viruses can resist the pelleting process but not subsequent irradiation or autoclaving, thus revealing a potential source of outbreaks in rodent facilities.

A Phase II Study of Irinotecan and Etoposide as Treatment for Refractory Metastatic Breast Cancer.

Lessons Learned: The combination of irinotecan and etoposide showed modest efficacy in terms of response rate in the refractory setting for patients with metastatic breast cancer.The studied dose and schedule of irinotecan and etoposide is very toxic, with >70% grade 3 or 4 treatment-related adverse events.

Background: As single agents, both irinotecan and etoposide have documented activity against breast cancer among patients who have received multiple lines of prior chemotherapy.

Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer.

Background: We previously reported prolonged progression-free survival and marginally prolonged overall survival among postmenopausal patients with hormone receptor-positive metastatic breast cancer who had been randomly assigned to receive the aromatase inhibitor anastrozole plus the selective estrogen-receptor down-regulator fulvestrant, as compared with anastrozole alone, as first-line therapy. We now report final survival outcomes.

Methods: We randomly assigned patients to receive either anastrozole or fulvestrant plus anastrozole.

Seroconversion of 1-year-old Mice to Murine Norovirus.

Rodent sentinel screening for adventitious pathogens is an integral part of many biomedical research institutes and universities that use rodents in research. Typical screening programs involving live sentinel animals typically purchase young SPF sentinel animals that are sampled and replaced quarterly. Previous reports suggest that mice as old as 6 mo are effective sentinels for various agents.

Ivermectin-compounded Feed Compared with Topical Moxidectin-Imidacloprid for Eradication of in Laboratory Mice.

Demodex musculi is a prostigmatid follicular mite that has rarely been reported in laboratory mice. Although prevalence of this species has not been assessed formally, we have found that many imported mouse strains from noncommercial sources harbor Demodex mites. To assess whether an acaricide can be used to eradicate this mite, infested immunocompromised mice were provided ivermectin-compounded (12 ppm) feed without restriction for 8 wk (n = 10), were treated topically with moxidectin and imidacloprid (MI; 3 and 13 mg/kg, respectively) weekly for 8 wk (n = 10), or remained untreated (n = 10).

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in Mutation Carriers.

Purpose: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer. We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene.

PCR Testing of Filter Material from IVC Lids for Microbial Monitoring of Mouse Colonies.

Testing sentinel animals exposed to soiled bedding from colony animals is the most common method used for health monitoring in rodent facilities. Although environmental sampling is being explored-and, in many cases, has been implemented-as an alternative, exhaust plenum sampling is not effective for all ventilated rack designs. This study evaluated PCR testing of filter paper from sentinel cages on ventilated racks.

Diagnosis of pneumocystis pneumonia in a 2-year-old King Charles Cavalier Spaniel using the polymerase chain reaction.

A 2-year-old, female spayed, King Charles Cavalier Spaniel was presented for evaluation of dyspnea, inappetence, and lethargy. Thoracic radiographs revealed a moderate diffuse interstitial lung pattern affecting the perihilar and caudodorsal lung fields, and an echocardiogram revealed severe pulmonary hypertension. A bronchoalveolar lavage (BAL) was performed, and cytology revealed mixed inflammation with cysts and trophozoites consistent with Pneumocystis.

Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci.

Objective: Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN.

A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies.

We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland.

Comparison of Antemortem and Environmental Samples for Zebrafish Health Monitoring and Quarantine.

Molecular diagnostic assays offer both exquisite sensitivity and the ability to test a wide variety of sample types. Various types of environmental sample, such as detritus and concentrated water, might provide a useful adjunct to sentinels in routine zebrafish health monitoring. Similarly, antemortem sampling would be advantageous for expediting zebrafish quarantine, without euthanasia of valuable fish.

Randomized trial of medroxyprogesterone acetate for the prevention of endometrial pathology from adjuvant tamoxifen for breast cancer: SWOG S9630.

The proliferative effect of adjuvant tamoxifen on the endometrium can potentially result in endometrial abnormalities, including cancer in postmenopausal women. We conducted a randomized, controlled trial to assess endometrial pathological diagnoses in postmenopausal women with early stage, ER-positive breast cancer without endometrial pathology at baseline. They were assigned to tamoxifen alone versus tamoxifen plus cyclical medroxyprogesterone acetate (MPA 10 mg for 14 days every 3 months) for 5 years.

Influence of Rack Design and Disease Prevalence on Detection of Rodent Pathogens in Exhaust Debris Samples from Individually Ventilated Caging Systems.

Sampling of bedding debris within the exhaust systems of ventilated racks may be a mechanism for detecting murine pathogens in colony animals. This study examined the effectiveness of detecting pathogens by PCR analysis of exhaust debris samples collected from ventilated racks of 2 different rack designs, one with unfiltered air flow from within the cage to the air-exhaust pathway, and the other had a filter between the cage and the air-exhaust pathway. For 12 wk, racks were populated with either 1 or 5 cages of mice (3 mice per cage) infected with one of the following pathogens: mouse norovirus (MNV), mouse parvovirus (MPV), mouse hepatitis virus (MHV), Helicobacter spp.

Bordetella pseudohinzii as a Confounding Organism in Murine Models of Pulmonary Disease.

A group studying acute lung injury observed an increased percentage of neutrophils in the bronchoalveolar lavage (BAL) fluid of mice. BAL was performed, and lung samples were collected sterilely from 5 C57BL/6 mice that had been bred inhouse. Pure colonies of bacteria, initially identified as Bordetella hinzii were cultured from 2 of the 5 mice which had the highest percentages of neutrophils (21% and 26%) in the BAL fluid.

Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer.

Introduction: Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients.