Citations

ABSTRACTObjectiveTo explore pre–hematopoietic stem cell transplant (HSCT) demographic, disease, and psychological factors predictive of future transplant regret and to determine post‐HSCT variables associated with regret.Patients and MethodsHSCT candidates participated in a prospective cohort study (June 2008–October 2013) examining health behaviors and HSCT outcomes, including completion of standardized surveys at pre‐HSCT (baseline) and 1‐year post‐HSCT. Cases were participants that endorsed regret at 1‐year post‐HSCT follow‐up, and controls were participants without regret at 1 year, matched on age, sex, and transplant type. For cases and controls, pre‐HSCT psychosocial evaluations were abstracted from the electronic health record and coded to determine the Psychosocial Assessment of Candidates for Transplantation score, psychosocial stressors, and mental health diagnoses. The association of selected factors with regret was estimated with odds ratios and 95% confidence intervals from conditional logistic regression models.ResultsAt post‐HSCT, 49 participants of 638 endorsed transplant regret (8%) and formed the case group; 98 controls were matched from remaining participants. Cases and controls were well matched on age (56.6 vs. 57.2 years), sex (both groups 34.7% female), and transplant type (both groups 81.6% autologous). After controlling for the number of hospitalizations and active treatment status, conditional logistic regression revealed that patients who endorsed regret were 3.7 times (95% CI = 1.37–9.69, p = 0.008) more likely to not be in remission compared to controls at 1‐year post‐HSCT.ConclusionMatched case–control analyses revealed that no pre‐HSCT variables collected during the pre‐HSCT evaluation period were predictive of transplant regret, while poorer outcomes at 1‐year after transplant were associated with regret.

Guideline-recommended screening programs exist for only a few single-cancer types, and these cancers represent less than one-half of all new cancer cases diagnosed each year in the U.S. In addition, these “single-cancer” standard of care (SoC) screening tests vary in accuracy, adherence, and effectiveness, though all are generally understood to lead to reductions in cancer-related mortality. Recent advances in high-throughput technologies and machine learning have facilitated the development of blood-based multi-cancer early detection (MCED) tests. The opportunity for early detection of multiple cancers with a single blood test holds promise in addressing the current unmet need in cancer screening. By complementing existing SoC screening, MCED tests have the potential to detect a wide range of cancers at earlier stages when patients are asymptomatic, enabling more effective treatment options and improved cancer outcomes. MCED tests are positioned to be utilized as a complementary screening tool to improve screening adherence at the population level, to broaden screening availability for individuals who are not adherent with SoC screening programs, as well as for those who may harbor cancers that do not have SoC testing available. Published work to date has primarily focused on test performance relating to sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). MCED tests will require approval through the pre-market approval pathway from the United States Food and Drug Administration. Additional studies will be needed to demonstrate clinical utility (i.e., improvements in health outcomes) and establish optimal implementation strategies, (i.e., testing intervals), follow-up and logistics of shared decision making. Here, we propose core attributes of MCED testing for which clinical data are needed to ideally position MCED testing for widespread use in clinical practice.

Purpose: This study aimed to compare long-term patient-reported outcomes in bowel and urinary domains between intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) for localized prostate cancer. Methods and Materials: Patients with clinical T1–T2 prostate cancer receiving IMRT or IMPT at a tertiary cancer center from 2015–2018 were analyzed to determine the changes in the prospectively collected bowel function (BF), urinary irritative/obstructive symptoms (UO), and urinary incontinence (UI) domains of EPIC-26. The mean changes in EPIC-26 scores were evaluated from pretreatment to 24 months post-radiotherapy for each modality. A score change >50% of the baseline standard deviation was considered a clinically meaningful change. Results: A total of 82 patients treated with IMRT (52.2%) and 56 patients treated with IMPT (53.3%) completed the questionnaire at baseline and 24 months post-RT. There were no baseline differences in domain scores between treatment modalities. At 24 months post-radiotherapy, there was a significant and clinically meaningful decline in the BF mean score in the IMRT cohort (−4.52 (range −50, 29.17), p = 0.003), whereas the decline in BF score did not reach clinical relevance or significance (−1.88 (range −37.5, 50), p = 0.046) when accounting for the Bonferroni adjustment in the IMPT cohort. A higher proportion of patients treated with IMRT had a clinically relevant reduction in BF when compared with IMPT (47.37% vs. 25.93%, p = 0.017). The mean changes in the UI and UO scores of the IMRT and IMPT cohorts were neither statically significant nor clinically relevant. Conclusions: IMPT leads to a smaller decrease in BF than IMRT at 24 months post-RT, while there was no differential effect on UO and UI.

Cardiovascular diseases (CVDs) are the leading cause of death in the world. A total of 17.5 million people died of CVDs in the year 2012, accounting for 31% of all deaths globally. Vertebrate animal models have been used to understand cardiac disease biology, as the cellular, molecular, and physiological aspects of human CVDs can be replicated closely in these organisms. Zebrafish is a popular model organism offering an arsenal of genetic tools that allow the rapid in vivo analysis of vertebrate gene function and disease conditions. It has a short breeding cycle, high fecundity, optically transparent embryos, rapid internal organ development, and easy maintenance. This review aims to give readers an overview of zebrafish cardiac biology and a detailed account of heart development in zebrafish and its comparison with humans and the conserved genetic circuitry. We also discuss the contributions made in CVD research using the zebrafish model. The first part of this review focuses on detailed information on the morphogenetic and differentiation processes in early cardiac development. The overlap and divergence of the human heart’s genetic circuitry, structure, and physiology are emphasized wherever applicable. In the second part of the review, we overview the molecular tools and techniques available to dissect gene function and expression in zebrafish, with special mention of the use of these tools in cardiac biology.

Intensive care units (ICUs) serve patients with life-threatening conditions. However, the availability of ICU resources remains scarce worldwide. Therefore, it is critical to conduct ICU outcome predictions at an early stage and promote efficient use of ICU resources. However, the current ICU outcome prediction methods have limitations such as unsatisfactory accuracy and dependence on resource-demanding laboratory tests or expert domain knowledge. In this research, we design a wavelet transform based additive convolutional neural network (WT-A-CNN) that requires only patients’ vital sign series and information at ICU admission for real-time ICU outcome predictions. The model is evaluated using a large real-world ICU database and outperforms state-of-the-art baselines on both ICU mortality and length-of-stay prediction tasks. Furthermore, the additive structure of the model can be used for model interpretation and analyzing which input signal is more useful for ICU outcome prediction for different patient cohorts. Our work provides an efficient tool for ICU outcome predictions, allowing healthcare providers to act promptly on patients at risk and reduce the negative impacts on patient outcomes.

Abstract The lung parenchyma comprises a large number of thin‐walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This chapter focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed. © 2011 American Physiological Society. Compr Physiol 1:1317‐1351, 2011.

Purpose The time to complete oncology pharmacist tasks is needed to determine workload and productivity. The Hematology/Oncology Pharmacy Association (HOPA) and the Hematology/Oncology Practice and Research Network (PRN) of the American College of Clinical Pharmacy (ACCP) partnered with the aim of establishing consensus on the time required to complete oncology pharmacy tasks. Methods Fifteen patient care tasks and 9 non-patient care tasks, commonly completed by oncology pharmacists were each assigned an average amount of time to be completed. This list was then converted into 24 statements and the Delphi survey method was utilized with an expert panel to arrive at consensus between December 2023 and February 2024. Consensus was defined as at least 75% agreement. The complete manuscript was endorsed by HOPA and ACCP Hematology/Oncology PRN. Results Thirty-three pharmacist-experts agreed to participate in this survey with all participating in round 1, and 29 (87.9%) participating in round 2. In round 1, 9 tasks achieved consensus, with 7 of these being classified as patient care associated. Seven statements reaching 65% but less than 75% agreement were deemed to reach borderline consensus. Eight statements failed to achieve at least 65% agreement and were modified based on respondent feedback. In round 2, 15 statements were included with all achieving consensus. At the completion of round 2, all 24 statements reached consensus, and the survey was deemed complete. Conclusion This project produced the first comprehensive consensus statements for the average time for a US-based oncology pharmacist to complete common patient and non-patient care-related tasks.

Purpose Venetoclax-based treatment for chronic lymphocytic leukemia (CLL) can be a logistically burdensome regimen due to extensive required monitoring of tumor lysis syndrome (TLS). The purpose of this study was to evaluate the feasibility and safety of pharmacist and registered nurse (RN) driven management of venetoclax ramp-up in CLL. Methods This was a prospective, pilot program for patients receiving venetoclax-based therapy for CLL. Patients had nine weekly visits during the first three cycles of therapy, of which five visits were independently performed by a pharmacist or RN. Laboratory tests to evaluate TLS were ordered and monitored independently by the RN in collaboration with clinicians (physician, nurse practitioner, physician assistant). Results Thirty CLL patients, median age 67 years, 73% treated in the frontline setting, started venetoclax between May 2022 and January 2023. After the initial three weeks of obinutuzumab treatment, TLS risk prior to venetoclax initiation had improved to low (93%), medium (3%), and high (3%). There was zero incidence of laboratory or clinical TLS by Howard criteria during the venetoclax ramp-up for all patients. Pharmacist and RNs performed 139 independent visits and monitored 197 sets of TLS labs. Conclusion Use of independent pharmacist and RN visits for toxicity checks and TLS monitoring during weekly venetoclax dose ramp-up did not lead to increased incidence of TLS in patients with CLL. These visits increased both access and efficiency within the CLL clinic. This concept has the potential to be applied in other cancer care settings with a variety of treatment regimens.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Common treatments following surgical resection include PD-1-targeting checkpoint inhibitors (pembrolizumab), as 20% of tumors are PD-L1 positive with or without systemic chemotherapy. Over the last several years, our laboratory has developed nano-immune conjugates (NIC) in which hydrophobic chemotherapy drugs like paclitaxel (PTX) and SN38, the active metabolite of irinotecan, are made water soluble by formulating them into albumin-based nanoparticles (nab) that are hydrophobically linked to various IgG1 monoclonal antibodies, creating an antigen-targetable nano-immune conjugate. To date, we have successfully tested PTX containing NICs linked to either VEGF- or CD20-targeted antibodies in two phase I clinical trials against multiple relapsed ovarian/uterine cancer or non-Hodgkin’s lymphoma, respectively. Herein, we describe a novel NIC created with either PTX or SN38 that is coated with anti-PD-L1-targeting antibodies for the treatment of a preclinical model of TNBC. In vitro testing suggests that the chemotherapy drug and antibody retain their toxicity and ligand binding capability in the context of the NIC. Furthermore, both the PTX and SN-38 NIC demonstrate superior anti-tumor efficacy relative to antibody and chemotherapy drugs alone in a PD-L1 + MDA-MB-231 human TNBC xenograft model, which could translate clinically to patients with TNBC.