Evaluation of hospital-onset bloodstream infections compared to central line...associated bloodstream infections at an acute, tertiary care hospital.

BACKGROUND: Central line...associated bloodstream infection (CLABSI) is the current benchmark used in HAI (Hospital-associated infection) surveillance and effective interventions have greatly reduced the incidence in recent years. However, bloodstream infection (BSI) continues to be a major source of morbidity and mortality in hospitals. Hospital-onset bloodstream infection (HOBSI), which includes central and peripheral line surveillance, may be a more sensitive indicator of preventable BSI. Our objective is to assess the impact of a change to HOBSI surveillance by comparing the incidence of BSIs using the National Health care and Safety Network LabID and BSI definitions compared to CLABSI. METHODS: Utilizing electronic medical charts, we determined if each blood culture met the HOBSI criteria according to the National Health care and Safety Network LabID and BSI definitions. We calculated the incidence rates (IRs) per 10,000 patient days for both definitions and compared them to the CLABSI rate per 10,000 patient days for the same period. RESULTS: The IR of HOBSI using the LabID definition was 10.25. Using the BSI definition, we found an IR of 3.77. The IR of CLABSI for the same period was 1.84. CONCLUSIONS: After excluding secondary BSIs, the HOBSI rate is still double that of the CLABSI rate. HOBSI surveillance is a more sensitive indicator of BSI than CLABSI, and thus a better target for monitoring effectiveness of interventions.

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML.

Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH1 inhibitor-naive patients with mIDH1R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) received olutasidenib monotherapy 150 mg twice daily in the pivotal cohort of this study. The median age of participants was 71 years (range, 32-87 years) and the median number of prior regimens received by patients was 2 (1-7). The rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) was 35%, and the overall response rate was 48%. Response rates were similar in patients who had, and who had not, received prior venetoclax. With 55% of patients censored at the time of data cut-off, the median duration of CR/CRh was 25.9 months. The median duration of overall response was 11.7 months, and the median overall survival was 11.6 months. Of 86 patients who were transfusion dependent at baseline, a 56-day transfusion independence was achieved in 29 (34%), which included patients in all response groups. Grade 3 or 4 treatment-emergent adverse events (≥10%) were febrile neutropenia and anemia (n = 31; 20% each), thrombocytopenia (n = 25; 16%), and neutropenia (n = 20; 13%). Differentiation syndrome adverse events of special interest occurred in 22 (14%) patients, with 14 (9%) grade ≥3 and 1 fatal case reported. Overall, olutasidenib induced durable remissions and transfusion independence with a well-characterized and manageable side effect profile. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognostic population of patients with mIDH1 R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02719574.

Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial.

BACKGROUND: Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aims for phase 1 of this phase 1/2 study were to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of olutasidenib, as monotherapy or in combination with azacitidine, in patients with acute myeloid leukaemia or myelodysplastic syndrome, harbouring mutant IDH1. METHODS: In this phase 1/2, multicentre, open-label clinical trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia or intermediate, high, or very high risk myelodysplastic syndrome harbouring mutant IDH1 at 18 study sites in the USA, Australia, France, and Spain. Other key eligibility criteria included Eastern Cooperative Oncology Group performance status 0-2 with adequate liver and renal function. The primary outcomes were dose-limiting toxicities and the maximum tolerated dose, maximum evaluated dose, and the recommended phase 2 dose of olutasidenib. Olutasidenib was administered orally in doses of 150 mg once daily, 150 mg twice per day, and 300 mg once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously daily for 7 days on, 21 days off. The study was ongoing at the data cutoff (Oct 2, 2019) and is registered with ClinicalTrials.gov, NCT02719574. FINDINGS: Patients were enrolled between Aug 8, 2016, and Nov 14, 2018. 78 patients received olutasidenib as monotherapy (n=32) or in combination with azacitidine (n=46). The median follow-up was 8·3 months (IQR 3·1-13·3) for monotherapy and 10·1 months (4·2-15·3) for combination therapy. 16 (50%) of 32 patients in the monotherapy group and 24 (52%) of 46 patients in the combination therapy group were women. Most patients were White (26 [81%] for monotherapy and 31 [67%] for combination therapy). No dose-limiting toxicities were reported in the dose-escalation cohorts and 150 mg twice per day was declared the recommended phase 2 dose on the basis of safety, pharmacokinetics and pharmacodynamics, and clinical activity. The most common (≥20%) grade 3-4 treatment-emergent adverse events with monotherapy were thrombocytopenia (nine [28%] of 32 patients), febrile neutropenia (seven [22%] of 32), and anaemia (seven [22%] of 32); and with combination therapy were thrombocytopenia (19 [41%] of 46), febrile neutropenia (13 [28%] of 46), neutropenia (13 [28%] of 46), and anaemia (nine [20%] of 46). 11 (34%) of 32 patients in the monotherapy group and nine (20%) of 46 patients in the combination therapy group died (most commonly from disease progression [three (9%) of 32 and four (9%) of 46]). No deaths were considered study-drug related. For patients with relapsed or refractory acute myeloid leukaemia, 41% (95% CI 21-64; nine of 22) receiving monotherapy and 46% (27-67; 12 of 26) receiving combination therapy had an overall response. For treatment-naive patients with acute myeloid leukaemia, 25% (1-81; one of four) receiving monotherapy and 77% (46-95; ten of 13) receiving combination therapy had an overall response. INTERPRETATION: Olutasidenib, with or without azacitidine, was well tolerated and showed meaningful clinical activity in patients with IDH1-mutated acute myeloid leukaemia. The results of this phase 1 study provide rationale for the continued evaluation of olutasidenib in multiple patient populations with myeloid malignancies. FUNDING: Forma Therapeutics.

Continuum of Care Screener: A Risk Mitigation Tool to Guide Decision Making When Environmental Factors Affect Service Delivery.

Navigating novel, unpredicted service disruptions can be complex and unparalleled. To effectively handle service interruptions, board certified behavior analysts (BCBAs®) must make sound clinical decisions, comply with the Behavior Analyst Certification Board's Ethics Code for Behavior Analysts (2020a), and critically engage in ongoing risk/benefit assessments for each individual client. Unfortunately, most BCBAs do not receive coursework, training, or fieldwork supervision in advanced risk mitigation. Those who have been practicing longer may have more experience in organizational systems and mitigating risk; however, half of all BCBAs have been certified in the last 5 years and two thirds have been certified in the last 7 years (BACB, 2021). This rapid growth of the profession poses significant challenges in navigating novel situations outside of the practitioner's scope of competency and learning history. In this article, we present a systematic formalized approach to risk management through an organizational behavior management lens. The article includes a screening tool, a summary of the model, and case examples of ongoing risk assessment during unexpected service disruptions. This screener is designed to help BCBAs think critically and systematically as they consider social and contextual factors across stakeholders, the client's behavioral status and treatment needs, state policy and law, and professional and ethical obligations during the decision-making process. Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-021-00672-7.

Pressure Injury Prevention for Complex Cardiovascular Patients in the Operating Room and Intensive Care Unit: A Quality Improvement Project.

PURPOSE: The purpose of our project was to examine the effect of an alternating pressure (AP) overlay on hospital-acquired pressure injury (HAPI) in high-risk cardiovascular surgical patients. PARTICIPANTS AND SETTING: This quality improvement (QI) initiative was conducted in a core group of 8 cardiovascular operating room (OR) suites and 1 cardiovascular surgical critical intensive care unit (ICU) in a large Indiana-based academic hospital. The sample comprised adult patients who underwent complex cardiovascular surgical procedures and those in the cardiovascular surgical ICU with extracorporeal membrane oxygenation (ECMO), ventricular assistive device (VAD), and undergoing heart and/or lung transplant, or open chest procedures. APPROACH: The AP overlay was placed on OR cardiovascular foam surfaces and on selected ICU support surfaces for patients who met inclusion criteria. We used a pre/postcomparative QI design to assess outcomes including OR-related HAPI rates, ICU aggregate unit HAPI data, related costs, and staff satisfaction during the 3-month project period. OUTCOMES: Operating room-related HAPIs were reduced from 8/71 (11%) preintervention to 0/147 (0%) postintervention (P = .008), resulting in a cost avoidance of $323,048 and positive staff satisfaction (mean = 3.85; 1- to 4-point Likert scale). No adverse outcomes occurred. Although not significant, ICU HAPI rates decreased from 10 to 7 pre/postintervention (P = .29), demonstrating a 14% HAPI reduction with a cost avoidance of $121,143. The ICU incidence density decreased from 3.57 to 3.24; however, there was no decrease in ICU monthly unit prevalence. Critical care staff satisfaction was positive (mean = 2.95; 1- to 4-point Likert scale) with most staff members preferring the AP overlay to a fluid immersion surface. A cost savings of 48% (AP overlay vs fluid immersion rental) was identified in the ICU. IMPLICATIONS FOR PRACTICE: We achieved fewer HAPIs and reduced costs and observed positive staff satisfaction, along with no adverse events with the use of the AP overlay. Further research is needed to determine the safety and efficacy of this device for this pressure injury prevention option for immobile patients in both the OR and the ICU.

Reimagining Relationship-Based Health Care in a Post-COVID World.

The US health care system has a long history of discouraging the creation and maintenance of meaningful relationships between patients and providers. Fee-for-service payment models, the 1-directional, paternalistic approach of care providers, electronic health records, anddocumentation requirements, all present barriers to the development of meaningful relationships in clinic visits. As patients and providers adopt and experiment with telemedicine and other systems changes to accommodate the impact of Coronavirus disease 2019, there is an opportunity to reimagine visits entirely-both office-based and virtual-and leverage technology to transform a unidirectional model into one that values relationships as critical facilitators of health and well-being for both patients and providers.

Placement of a Double-Lumen Endotracheal Tube Using a Combined Bronchoscopy and Fluoroscopy Technique: A Case Report.

Bronchial artery embolization (BAE) is a well-established intervention for hemoptysis that requires airway management by a trained anesthesiologist. The use of fluoroscopic guidance for positioning a double-lumen endotracheal tube (DLT) has been described in previous studies. The case presented illustrates a combined fluoroscopic- and bronchoscopic-guided approach for positioning a DLT in a patient with active pulmonary hemorrhage causing obstruction of views on bronchoscopy. This combined technique proved valuable in a situation marked by high clinical urgency.

Incorporating preauthorization into antimicrobial stewardship pharmacist workflow reduces Clostridioides difficile and gastrointestinal panel testing.

OBJECTIVE: To evaluate whether incorporating mandatory prior authorization for Clostridioides difficile testing into antimicrobial stewardship pharmacist workflow could reduce testing in patients with alternative etiologies for diarrhea. DESIGN: Single center, quasi-experimental before-and-after study. SETTING: Tertiary-care, academic medical center in Ann Arbor, Michigan. PATIENTS: Adult and pediatric patients admitted between September 11, 2019 and December 10, 2019 were included if they had an order placed for 1 of the following: (1) C. difficile enzyme immunoassay (EIA) in patients hospitalized >72 hours and received laxatives, oral contrast, or initiated tube feeds within the prior 48 hours, (2) repeat molecular multiplex gastrointestinal pathogen panel (GIPAN) testing, or (3) GIPAN testing in patients hospitalized >72 hours. INTERVENTION: A best-practice alert prompting prior authorization by the antimicrobial stewardship program (ASP) for EIA or GIPAN testing was implemented. Approval required the provider to page the ASP pharmacist and discuss rationale for testing. The provider could not proceed with the order if ASP approval was not obtained. RESULTS: An average of 2.5 requests per day were received over the 3-month intervention period. The weekly rate of EIA and GIPAN orders per 1,000 patient days decreased significantly from 6.05 ± 0.94 to 4.87 ± 0.78 (IRR, 0.72; 95% CI, 0.56-0.93; P = .010) and from 1.72 ± 0.37 to 0.89 ± 0.29 (IRR, 0.53; 95% CI, 0.37-0.77; P = .001), respectively. CONCLUSIONS: We identified an efficient, effective C. difficile and GIPAN diagnostic stewardship approval model.

Rare Abdominal Wall Metastasis following Curative Resection of Gastric Cancer: What Can Be Learned from the Use of Percutaneous Catheters?

In cancer care, tissue seeding after curative resections is a known potential complication, despite precautions taken during surgical treatment. We present an uncommon case of an abdominal wall metastasis along the tract of a surgical drain following gastrectomy for gastric adenocarcinoma. To our knowledge, this is the first case of such an occurrence in the setting of a negative staging peritoneal lavage. Aside from the rarity of such a recurrence, this instance highlights an opportunity to reevaluate best practices with regard to the extent of coverage of postoperative salvage radiotherapy. The oncologic patient provides many challenges and may require multiple catheters for drainage and at times infusion of nutrition or therapeutic agents. These foreign bodies should be scrutinized both clinically and radiographically, as they may create vulnerabilities in keeping malignant diseases contained and controlled. We provide a review of the literature with reasonable treatment options for the benefit of future patients.

Transarterial Radioembolization Treatment of Pancreatic Cancer Patients with Liver-Dominant Metastatic Disease Using Yttrium-90 Glass Microspheres: A Single-Institution Retrospective Study.

PURPOSE: To retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 (90Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease. MATERIALS AND METHODS: This retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months. RESULTS: Median overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5-87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0-86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0-84.1 months). Grade 1-2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1-2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment. CONCLUSIONS: TARE with 90Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer.

Ablation of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is the second most common primary liver cancer but represents only a small portion of all primary liver cancers. At the time of diagnosis, patients are often not surgical candidates due to tumor burden of other comorbidities. In addition, there is a very high rate of tumor recurrence after resection. Local regional therapies, specifically ablative therapies of radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation, have proven to be beneficial with other hepatic tumors. The purpose of this review is to provide an overview and update of the medical literature demonstrating ablative therapy as a treatment option for intrahepatic cholangiocarcinoma.

Function of the Medical Team Quarterback: Patient, Family, and Physician Perspectives on Team Care Coordination in Patient- and Family-Centered Primary Care.

CONTEXT: Patient- and family-centered care (PFCC) literature is growing, but few reports present patient, caregiver, and practitioner perspectives about care coordination in a team-based model. OBJECTIVE: To understand the patient's, caregiver's, and physician's ideal forms of PFCC, we investigated the function of the medical team quarterback, who coordinates and advocates for appropriate care, and probed to understand how the quarterback works with a team to contribute to ideal PFCC. DESIGN AND MAIN OUTCOME MEASURES: Nine focus groups with 92 participants were held in 3 major cities. Patients (n = 35) and family members (n = 36) were recruited through market research groups. Physicians (n = 21) were recruited by the American College of Physicians. Focus group transcripts were analyzed and coded using inductive analysis. RESULTS: The quarterback emerged as an important function for addressing care gaps and improving the care experience. We identified 6 themes articulated by participants that defined the role of a medical team quarterback: Overseeing care; coordinating diagnoses, tests, and treatments; advocating for patients; identifying and respecting patient values; proactively communicating; and solving problems. Patients and family members in our sample were open to different members of the care team acting as quarterback in coordination with the physician. CONCLUSION: Medical team quarterbacks were perceived as enhancing team-based care by facilitating the coordination/communication that is critical to PFCC. Patients and family members acknowledged that PFCC can be delivered by different members of the medical team if the care felt organized and coordinated with the primary care physician.

Strategies for the successful implementation of disinfecting port protectors to reduce CLABSI in a large tertiary care teaching hospital.

Disinfecting port protectors are a supplement to the central line-associated bloodstream infection prevention bundle as an optional recommendation from the Centers for Disease Control and Prevention. Despite evidence of effectiveness, few centers have successfully reported systematic, sustained implementation of these devices. In this article, we discuss a successful implementation in a large tertiary care teaching hospital, using an evidence-based, multidisciplinary approach. Infection prevention; Bacteremia; Ethanol caps; Bundle measures; Quality improvement; Hub infection.

Actions and processes that patients, family members, and physicians associate with patient- and family-centered care.

BACKGROUND: Patient- and family-centered care (PFCC) is increasingly linked to improved communication, care quality, and patient decision making. However, in order to consistently implement and study PFCC, health care systems and researchers need a solid evidentiary base. Most current definitions and models of PFCC are broad and conceptual, and difficult to translate into measurable behaviors and actions. This paper provides a brief overview of all actions that focus group respondents associated with PFCC in ambulatory (outpatient) care settings and then explores actions associated with the concept of "dignity and respect" in greater detail. METHODS: We conducted nine focus groups with patients, family members, and physicians in three metropolitan regions across the United States. Group discussions were transcribed and analyzed using a thematic analysis approach. RESULTS: We identified 14 domains and 47 specific actions that patients, family members, and physicians associate with PFCC. In addition to providing a detailed matrix of these domains and actions, this paper details the actions associated with the "dignity and respect" concept. Key domains identified under "dignity and respect" include: 1) building relationships, 2) providing individualized care, and 3) respecting patients' time. Within these domains we identified specific actions that break down these abstract ideas into explicit and measurable units such as taking time, listening, including family, and minimizing wait times. We identified 9, 6, and 3 specific actions associated, respectively, with building relationships, providing individualized care, and respecting patients' time. CONCLUSIONS: Our work fills a critical gap in our ability to understand and measure PFCC in ambulatory care settings by breaking down abstract concepts about PFCC into specific measurable actions. Our findings can be used to support research on how PFCC affects clinical outcomes and develop innovative tools and policies to support PFCC.

Complication of hemothorax after CT-guided percutaneous biopsy of herniated liver masquerading as a pulmonary mass.

Hemothorax is a rare complication of percutaneous needle biopsy in the chest at a rate of 0.092%. Rarer yet is diaphragm injury with herniation of intra-abdominal organs. The patient was a 56-year-old female undergoing evaluation for primary lung cancer diagnosis requiring lung mass biopsy. The largest pulmonary nodule was biopsied, which abutted the right hemidiaphragm with the complication of hemothorax. Angiography demonstrated that the source of bleeding was not attributed to intercostal artery injury. Pathology revealed that benign hepatic tissue was sampled. Based on the pathology results, angiographic findings, and detailed review of cross-sectional imaging, the tissue is consistent with herniated liver through the right hemidiaphragm mistaken to be a pulmonary nodule.

Using the Albumin-Bilirubin (ALBI) grade as a prognostic marker for radioembolization of hepatocellular carcinoma.

BACKGROUND: The Child-Pugh (CP) class is a commonly used scoring system to measure liver function in patients with hepatocellular carcinoma (HCC). We correlate the Albumin-Bilirubin (ALBI) grading system and CP to overall survival in our HCC patients receiving radioembolization. METHODS: We retrospectively evaluated patients who received radioembolization for HCC between the years 2009-2014. We evaluated the albumin and bilirubin levels in our patients prior to receiving their first (n=124) radioembolization. The ALBI grades were calculated from these data with the formula (log10 bilirubin ×0.66) + (albumin × -0.085) and correlated to outcomes using Mantel-Cox Log analysis. These statistical comparisons were duplicated with CP classes. RESULTS: Median survival differences between CP class A and B and between ALBI grade 1 and 2 were 4.7 and 9.9 months, respectively. A subset of ALBI grades 1 and 2 were identified within our CP class A patients with a median survival difference of 9.9 months. CONCLUSIONS: ALBI is a more sensitive marker of liver function than CP in the setting of mild dysfunction. Using ALBI, we identified a subset of patients that have significantly better outcomes from Y-90 radioembolization than previously identified with CP.

Impacting Delirium in the Trauma ICU Utilizing the ICU Liberation Collaborative Benchmark Report.

Delirium is a frequent complication of intensive care unit (ICU) admissions, manifesting as acute confusion with inattention and disordered thinking. Patients in the ICU who develop acute delirium are more likely to experience long-term disability and mortality. The Society of Critical Care Medicine published guidelines for the management of pain, agitation, and delirium (PAD) in the ICU in 2013. Based on these PAD guidelines, the ABCDEF bundle was created. Research is lacking on how adherence to the ABCDEF bundle elements impacts specific populations such as trauma patients. This represents a significant gap for patients whose multisystem injuries and comorbidities add a higher level of complexity to their care and outcomes. The medical ICU at a large community hospital participated in a 2-year quality improvement project as part of the Society of Critical Care Medicine's ICU Liberation Collaborative. However the organization's trauma ICU (TICU) was excluded from the study. The purpose of this study was to conduct a baseline assessment of trauma patient records to determine which bundle elements were already being applied in the TICU, and if the resources required for implementing the full ABCDEF bundle would be beneficial to the TICU patient outcomes. Benchmark data from the organization's participation in the ICU Liberation Collaborative quality improvement project served as the primary source of evidence. Analysis revealed strengths and opportunities for improvement. Incidence of delirium remained unchanged and far below national averages, indicating the need for further investigation into practices to verify this finding. An opportunity was identified to expand implementation of certain elements of the ABCDEF bundle in the trauma ICU. There is an opportunity for nurses to take the lead in improving patient outcomes. With improved education, evidence-based assessment tools, and best practice guidelines, nurses can help decrease the incidence of delirium by as much as 30%.

Principles for Patient and Family Partnership in Care: An American College of Physicians Position Paper.

In this position paper, the American College of Physicians (ACP) examines the rationale for patient and family partnership in care and reviews outcomes associated with this concept, including greater adherence to care plans, improved satisfaction, and lower costs. The paper also explores and acknowledges challenges associated with implementing patient- and family-centered models of care. On the basis of a comprehensive literature review and a multistakeholder vetting process, the ACP's Patient Partnership in Healthcare Committee developed a set of principles that form the foundation for authentic patient and family partnership in care. The principles position patients in their rightful place at the center of care while acknowledging the importance of partnership between the care team and patient in improving health care and reducing harm. The principles state that patients and families should be treated with dignity and respect, be active partners in all aspects of their care, contribute to the development and improvement of health care systems, and be partners in the education of health care professionals. This paper also recommends ways to implement these principles in daily practice.

Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study.

Duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-δ and -γ, was evaluated in a Phase 1 study in advanced hematologic malignancies, which included expansion cohorts in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment-naïve (TN) CLL. Per protocol, TN patients were at least 65 years old or had a del(17p)/TP53 mutation. Duvelisib was administered twice daily (BID) in 28-day cycles at doses of 8-75 mg in RR patients (n = 55) and 25 mg in TN patients (n = 18.) Diarrhea was the most common nonhematologic AE (TN 78%, RR 47%); transaminase elevations the most frequent lab-abnormality AE (TN 33.3%, RR 30.9%); and neutropenia the most common ≥grade 3 AE (RR 44%, TN 33%). The overall response rates were 56.4% for RR patients (1.8% CR, 54.5% PR) and 83.3% for TN patients (all PRs); median response duration was 21.0 months in RR patients but was not reached for TN patients. Based upon phase 1 efficacy, pharmacodynamics, and safety, duvelisib 25 mg BID was selected for further investigation in a phase 3 study in RR CLL/SLL.

Viral hepatitis associated hepatocellular carcinoma outcomes with yttrium-90 radioembolization.

BACKGROUND: Viral associated (VA) malignancies have recently been correlated with improved outcomes. We sought to evaluate outcomes of patients with hepatocellular carcinoma (HCC) with and without viral hepatitis (hepatitis B and C) treated with lobar yttrium-90 radioembolization (Y-90 RE). METHODS: After IRB approval, an institutional database of patients with HCC who received RE between 2009-2014 was queried and 99 patients were identified that received a total of 122 lobar RE. Charts were reviewed to capture previous treatments, viral hepatitis status, α-fetoprotein values (AFP), Child-Pugh class (CP), albumin-bilirubin score (ALBI), portal vein thrombosis (PVT), volumes treated and doses delivered. Comparison was made with Chi-square and Mann-Whitney U test. Intrahepatic control (IHC), extrahepatic control (EHC), progression free survival (PFS), and overall survival (OS) were calculated according to the Kaplan-Meier method stratified by cause of underlying liver disease (viral vs. non-viral) and survival differences were assessed via the log-rank test. Hazard ratios were calculated using Cox regression. RESULTS: Median follow up for VA HCC and non-VA (NVA) HCC patients was 10.9 months (range, 0.8-46.7 months) and 11.8 months (range, 1.1-62.8 months), respectively. Patients with VA HCC (n=44) were younger (P<0.001) and had smaller pretreatment liver volumes (P<0.001); however, there was no difference with respect to gender, pre-treatment AFP, CP, ALBI, PVT, extrahepatic disease, previous treatment, or dose delivered. Median doses for VA and NVA HCC patients were 129.5 Gy (range, 90-215.8 Gy) and 131 Gy (range, 100.9-265 Gy), respectively (P=0.75). One year IHC showed a strong trend to better control for VA HCC at 67% versus 34% for NVA HCC (P=0.067) but 1 year EHC was significantly worse at 63% for VA HCC versus 86% for NVA HCC (P=0.027). There were no significant differences in survival, with a 1-year PFS of 45% for VA HCC versus 31% for NVA HCC (P=0.56) and 1 year OS of 46% versus 55% (P=0.55). Patients that received salvage treatments, CP A, no PVT, and those without extrahepatic disease had improved OS. CONCLUSIONS: Patients with VA HCC had a trend to improved IHC and significantly worse EHC. Prospective investigation of novel systemic therapies following Y-90 RE in patients with VA HCC is warranted to potentially further extend survival in VA HCC patients by addressing extra-hepatic disease.