Empowering Night Shift Through Building a Stronger Foundation for Shared Governance.

A 341-bed Magnet® designated facility expanded its shared governance structure by incorporating a night shift council. The formation of this council allowed for more robust communication and collaboration between disciplines among night shift staff while increasing engagement scores. The council has established many initiatives to support night shift staff that can be adapted for use by other hospitals and health systems interested in expanding their shared governance structure.

Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors.

Immunotherapy is the standard of care for several cancers and the field continues to advance at a rapid pace, with novel combinations leading to indications in an increasing number of disease settings. Durable responses and long-term survival with immunotherapy have been demonstrated in some patients, though lack of initial benefit and recurrence after extended disease control remain major hurdles for the field. Many new combination regimens are in development for patients whose disease progressed on initial immunotherapy.

A phase I study of veliparib with cyclophosphamide and veliparib combined with doxorubicin and cyclophosphamide in advanced malignancies.

Purpose: Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C.

Methods: Objectives were to establish the maximum tolerated dose (MTD) of the combinations, characterize V pharmacokinetics (PK) in the presence and absence of C, measure PAR in peripheral blood mononuclear cells (PBMCs) and γH2AX in circulating tumor cells (CTCs).

Belowground productivity varies by assessment technique, vegetation type, and nutrient availability in tidal freshwater forested wetlands transitioning to marsh.

Wetlands along upper estuaries are characterized by dynamic transitions between forested and herbaceous communities (marsh) as salinity, hydroperiod, and nutrients change. The importance of belowground net primary productivity (BNPP) associated with fine and coarse root growth also changes but remains the dominant component of overall productivity in these important blue carbon wetlands. Appropriate BNPP assessment techniques to use in various tidal wetlands are not well-defined, and could make a difference in BNPP estimation.

Neoadjuvant Therapy for Melanoma: A U.S. Food and Drug Administration-Melanoma Research Alliance Public Workshop.

Tremendous progress has been made in treating patients with metastatic melanoma over the past decade. In that timeframe, the FDA has approved 12 novel treatments for patients with advanced unresectable melanoma, comprising both kinase-targeted therapies and immune checkpoint inhibitors (ICI), and five treatments for adjuvant (postoperative) use in patients with high-risk resectable stage III melanoma. It is not known whether outcomes can be further improved by administering kinase inhibitors or ICI in the neoadjuvant (presurgical) setting in patients with high-risk resectable melanomas.

A Machine-Learning Approach to Identify a Prognostic Cytokine Signature That Is Associated With Nivolumab Clearance in Patients With Advanced Melanoma.

Lower clearance of immune checkpoint inhibitors is a predictor of improved overall survival (OS) in patients with advanced cancer. We investigated a novel approach using machine learning to identify a baseline composite cytokine signature via clearance, which, in turn, could be associated with OS in advanced melanoma. Peripheral nivolumab clearance and cytokine data from patients treated with nivolumab in two phase III studies (n = 468 (pooled)) and another phase III study (n = 158) were used for machine-learning model development and validation, respectively.

A phase I trial of MK-2206 and hydroxychloroquine in patients with advanced solid tumors.

Purpose: Given the evidence that coordinate inhibition of AKT induces autophagy, we studied the combination of the AKT inhibitor, MK-2206 with hydroxychloroquine (HCQ) in patients with advanced solid tumors.

Methods: Patients were treated with weekly MK-2206 (135 mg or 200 mg) plus HCQ (200 mg, 400 mg or 600 mg BID).

Results: Thirty-five patients were enrolled across 5 dose levels.

A phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors.

Background AT-101 is a BH3 mimetic that inhibits the heterodimerization of Bcl-2, Bcl-xL, Bcl-W, and Mcl-1 with pro-apoptotic proteins, thereby lowering the threshold for apoptosis. This phase I trial investigated the MTD of AT-101 in combination with paclitaxel and carboplatin in patients with advanced solid tumors. Methods Patients were treated with AT-101 (40 mg) every 12 h on days 1, 2 and 3 of each cycle combined with varying dose levels (DL) of paclitaxel and carboplatin [DL1: paclitaxel (150 mg/m) and carboplatin (AUC 5) on day 1 of each cycle; DL2: paclitaxel (175 mg/m) and carboplatin (AUC 6) on day 1 of each cycle].

Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.

Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes.

A Blueprint to Advance Colorectal Cancer Immunotherapies.

Immunotherapy is rapidly becoming a standard of care for many cancers. However, colorectal cancer had been generally resistant to immunotherapy, despite features in common with sensitive tumors. Observations of substantial clinical activity for checkpoint blockade in colorectal cancers with defective mismatch repair (microsatellite instability-high tumors) have reignited interest in the search for immunotherapies that could be extended to the larger microsatellite stable (MSS) population.

A Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of Pictilisib in Combination with Erlotinib in Patients with Advanced Solid Tumors.

Background: Epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K) are involved in the proliferation and survival of many cancer types. Enhanced antitumor activity may be achieved through combined inhibition of these pathways. We report results for pictilisib (GDC-0941, a class I pan-PI3K inhibitor) plus erlotinib (an EGFR tyrosine kinase inhibitor) in patients with advanced solid tumors.

Bone marrow tolerance during postoperative chemotherapy in colorectal carcinomas.

Background: This study seeks to quantify and compare bone marrow tolerance during postoperative chemotherapy therapy between rectal cancer colon cancer patients. During rectal cancer treatment, patients receive neoadjuvant chemoradiation (CRT) irradiation which can exacerbate the hematologic toxicity (HT) via incidental irradiation of the pelvic bone marrow (PBM) during myelosuppressive postoperative chemotherapy. In contrast, colon cancer patients receive the same postoperative myelosuppressive chemotherapy but do not routinely receive preoperative chemoradiation therapy.

Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.

Background: Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer.

Neoadjuvant Chemotherapy and Adjuvant Chemoradiation Therapy in the Treatment of Resected Gastric Adenocarcinoma: A Case Series.

The treatment of gastric cancer requires a multimodal approach to decrease the risk of locoregional and distant recurrence. The optimal timing of chemotherapy, surgery, and radiation therapy continues to be explored in ongoing trials. In the United States, surgical resection is often followed by adjuvant chemoradiation therapy or by a combination of neoadjuvant and adjuvant chemotherapy.

First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors.

Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database.

Background: While mortality in the United States has decreased for most cancers, mortality from combined hepatocellular liver cancer and intrahepatic cholangiocarcinoma (ICC) has increased and ranked 1st in annual percent increase among cancer sites. Because reported statistics combine ICC with other liver cancers, mortality rates of cholangiocarcinoma (CCA) remain unknown. This study is to determine CCA mortality trends and variation based on national data.

Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers.

Background: The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important.

Methods: A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors.

Inter-Annual Variability of Area-Scaled Gaseous Carbon Emissions from Wetland Soils in the Liaohe Delta, China.

Global management of wetlands to suppress greenhouse gas (GHG) emissions, facilitate carbon (C) sequestration, and reduce atmospheric CO2 concentrations while simultaneously promoting agricultural gains is paramount. However, studies that relate variability in CO2 and CH4 emissions at large spatial scales are limited. We investigated three-year emissions of soil CO2 and CH4 from the primary wetland types of the Liaohe Delta, China, by focusing on a total wetland area of 3287 km2.

Long-Term Bone Marrow Suppression During Postoperative Chemotherapy in Rectal Cancer Patients After Preoperative Chemoradiation Therapy.

Purpose/objective(s): To quantify ensuing bone marrow (BM) suppression during postoperative chemotherapy resulting from preoperative chemoradiation (CRT) therapy for rectal cancer.

Methods And Materials: We retrospectively evaluated 35 patients treated with preoperative CRT followed by postoperative 5-Fluorouracil and oxaliplatin (OxF) chemotherapy for locally advanced rectal cancer. The pelvic bone marrow (PBM) was divided into ilium (IBM), lower pelvis (LPBM), and lumbosacrum (LSBM).

Early vs. Late Chemoradiation Therapy and the Postoperative Interval to Adjuvant Therapy Do Not Correspond to Local Recurrence in Resected Pancreatic Cancer.

Objective: Standard postoperative therapy for pancreatic cancer consists of both chemotherapy alone and chemoradiation. We sought to investigate whether the sequence of chemotherapy and chemoradiation and overall time to initiation of adjuvant therapy would impact local vs. distant recurrence.

HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators.

Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag), and their synthesis is dependent upon frameshifting. This ensures that a strictly regulated ratio of structural proteins and enzymes, which is critical for HIV-1 replication and viral infectivity, is maintained during protein synthesis.

Hepatocellular Carcinoma Without Cirrhosis Presenting With Hypercalcemia: Case Report and Literature Review.

Background: Hepatocellular carcinoma (HCC) in non-cirrhotic livers is an uncommon finding and can present insidiously in patients. Another uncommon finding in HCC, and one of poor prognosis, is the presence of paraneoplastic diseases such as hypercalcemia. We report a case of a 66-year-old previous healthy Filipina woman who after routine laboratory evaluation was discovered to have hypercalcemia as the first sign of an advanced HCC without underlying cirrhosis.

Effect of nutrients and salinity pulses on biomass and growth of Vallisneria americana in lower St Johns River, FL, USA.

We determined the interactive effects of nutrient loading and salinity pulsing on Vallisneria americana Michx., the dominant submerged aquatic vegetation species in the lower St Johns River (LSJR), FL, USA, and its associated algal community. Five hundred and ninety 6-inch diameter intact plant plugs of Vallisneria were collected from the LSJR in March 2003 and transported to US Geological Survey mesocosm facilities in Lafayette, LA, USA.

A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511).

Objectives: Veliparib (V) potentiated therapeutic efficacy of cisplatin (C) and etoposide (E) in preclinical models of SCLC. We conducted this phase 1 study to establish the safety of the combination in human subjects.

Materials And Methods: The study employed the 3+3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75 mg/m(2) on day 1) and E (100mg/m(2) on days 1-3) in a 21-day cycle.

Refeeding syndrome in a vegan patient with stage IV gastric cancer: a novel case.

The refeeding syndrome encompasses the complex physiologic state that occurs in malnourished patients who receive nutrition after a period of decreased oral intake. The hallmark of the syndrome is hypophosphatemia, though other electrolyte imbalances and severe fluid shifts are commonly involved. Patients with newly diagnosed malignancies and those undergoing treatment for malignancies are at increased risk for developing the refeeding syndrome, however there are few reported cases or other data in the oncology literature regarding this syndrome in cancer patients.