Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial.

PURPOSE: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

The evolution of clinical outcomes in metastatic pancreatic adenocarcinoma: a 10-year experience at a tertiary referral center.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the US. Recent studies have demonstrated survival benefits for FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and Gem/nab-P (gemcitabine/nab-paclitaxel) over gemcitabine. We aimed to evaluate the clinical outcomes of mPDAC before and after incorporating these newer regimens into the clinical practice. METHODS: A retrospective study of patients with mPDAC at our institution between 2009 and 2018, who were followed up until December 2019. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier survival analysis. Univariate and multivariable Cox regression analyses were used to explore predictors of survival. RESULTS: A total of 394 patients with mPDAC were included: 122 (31%) were diagnosed 2009-2013 and 272 (69%) 2014-2018. In 2009-2013 cohort vs. 2014-2018 cohort, the median OS and PFS were similar (4 vs. 3.6 months, P = 0.5) and (2.3 vs. 2.5 months, P = 0.41), respectively. Age, ECOG-PS >1, serum albumin, neutrophil-to-lymphocyte ratio, and platelets-to-lymphocyte ratio were independent predictors of better OS. CONCLUSIONS: In this study of real-world data, the median OS and PFS for all patients with mPDAC were equivalent before and after incorporating newer treatment regimens into the clinical practice.

Biopsychosocial Pain Management and its Effect on Postoperative Opioid Use.

INTRODUCTION: Medical use and overuse of opioids have become an increasing problem over the past several decades. Postoperative pain control is the strongest indication for the use of opioid analgesics. Previous studies have demonstrated benefit from complementary and alternative therapy (CAT) for postoperative pain relief. A prior study conducted by Riswold et al. found that a unit staff training session on CAT improved patient experiences postoperatively following total joint replacement. The study was limited in that it did not examine if there were any changes in opioid usage following this intervention. METHODS: This study is a continuation of the Riswold et al. study on CAT training intervention. In July 2017, a four-hour staff training session on alternative comfort measures and pain medication administration took place. Opioid administration data was extracted from the PYXIS software for all patients who had received more than three opioid administrations across their hospital stay in the three months prior to CAT training and the three months post-training. Opioid administrations were converted to total oral morphine equivalents. The pre- and post-intervention groups were compared using independent sample t-tests using SPSS software. RESULTS: Statistically significant reduction of total oral morphine equivalents occurred following CAT training intervention (p=.034, CI 2.76, 69.81). Average oral morphine equivalents per day (p=0.023, CI 1.26, 16.57) and per administration (p=0.00048, CI 0.64, 2.25) also were significantly reduced following the CAT training intervention. CONCLUSION: This study strengthens the findings of prior studies, showing that CAT can improve patient satisfaction while also reducing overall opioid burden for post-surgical patients.

Post-injury and resolution response to repetitive inhalation exposure to agricultural organic dust in mice.

Inhalation of organic dusts in agricultural environments causes airway inflammatory diseases. Despite advances in understanding the airway response to dust-induced inflammation, less is known about the transition from lung injury to repair and recovery. The objective of this study was to define the post-inflammation homeostasis events following organic dust-induced lung injury. Using an established protocol, mice were intranasally treated with swine confinement facility organic dust extract (ODE) daily for 3 weeks (repetitive exposure) or treated daily with ODE for 3 weeks followed by no treatment for 1-4 weeks (recovery period) whereupon lavage fluid, lung tissue, and sera were processed. During recovery period, a significant decrease was observed in ODE-induced neutrophil levels after 1 week, lymphocytes at 2 weeks, and macrophages at 4 weeks in the lavage fluid. ODE-induced lung cellular aggregates and bronchiolar compartment inflammation were diminished, but persisted for 4 weeks post-injury. Alveolar inflammation resolved at 3 weeks. ODE-induced lung neutrophils were cleared by 3 weeks, B-cells by 2 weeks, and CD3+CD4+ and CD3+CD8+ T cells by 4 week recovery period. Collectively, these results identify important processes during recovery period following agricultural dust-induced inflammation, and present possible strategies for improving lung repair and resolution.