Citations

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.

Abstract Background Adults with congenital heart disease (ACHD) frequently experience gaps in lifelong ACHD specialty care, leading to preventable complications, hospitalizations, and premature mortality. However, effective, scalable, accessible, and sustainable strategies to reduce these gaps are lacking. Digital health offers potential solutions but requires a rigorous scientific approach in its design to address the needs of the target population. Objective To describe the development of a theory-based, community co-designed digital health intervention to improve lifelong ACHD care. Methods We integrated theory-based behavioral frameworks, semi-structured qualitative interviews with patients and clinicians, and a community-engaged approach to develop a digital health intervention for ACHD. The primary behavioral target was completing an ACHD specialist appointment. We conducted Capability, Opportunity, Motivation, and Behavior (COM-B)-guided semi-structured interviews with ACHD patients and clinicians to identify barriers to specialized care amenable to a digital intervention and patient-centered goals for the digital tool. The community partners helped develop key intervention objectives, create a theory-driven framework, and specify how each intervention component targets specific COM-B barriers. Results We interviewed 54 participants (37 ACHD patients and 17 clinicians) and engaged 21 community partners representing 4 advocacy organizations. Design objectives emphasized addressing patient loneliness, ensuring accessibility and credibility, and enabling scalability while centering patient perspectives. Participants identified four priorities: providing credible resources, uplifting patient voices, customizing to patient needs, and centering positivity and joy. The digital tool, named by community partners as Empower My Congenital Heart (EMCH), was designed within the web- and mobile-based, Apple- and Android-compatible, Eureka Digital Research platform (University of California, San Francisco). Key intervention components included educational modules, peer support, appointment planning nudges, and a digital medical passport. The EMCH’s theory-driven framework specifies how each intervention component targets specific COM-B barriers to specialized ACHD care. Conclusions The theory-driven, community co-designed EMCH digital tool is a rapidly scalable approach to improve guideline-recommended specialized ACHD care. Future studies will evaluate the acceptability, feasibility, effectiveness, and implementation outcomes to provide insight into a novel tool to reduce preventable morbidity and mortality in ACHD. Trial Registration The National Clinical Trial number for this study is NCT06581484 .

Encephalopathy is a disturbance in neurologic function. It is commonly attributed to infectious and inflammatory etiologies but encompasses a wide differential. Hypereosinophilic syndrome (HES) is a rare cause of encephalopathy that is associated with underlying infection or malignancy. We present a pediatric patient who experienced several days of worsening encephalopathy and neurological deterioration associated with influenza B infection and hypereosinophilia. A thorough workup ultimately revealed a diagnosis of HES secondary to B cell acute lymphoblastic leukemia (B-ALL). This case exemplifies the importance of maintaining a broad approach to the diagnostic evaluation, treatment, and management of encephalopathy.

ABSTRACT Background Facet Joint Septic Arthritis (FJSA) is an infection of the spinal facet joints, for which previously described imaging findings are non‐specific. We present MRI findings of 20 patients who underwent facet biopsy for possible FJSA. Materials and Methods An internal database was reviewed for cases who underwent image‐guided spinal facet biopsy for possible infection and had pre‐biopsy contrast‐enhanced MRI. Cases were categorized as biopsy FJSA positive or negative and MRI was reviewed for synovitis, bone marrow enhancement, epidural phlegmon/abscess, and paraspinal muscle enhancement. The MRI findings were considered extensive if the involvement of the posterior paraspinal muscles spanned at least two vertebral bodies in the craniocaudal direction and at least half the length of the muscles in the anterior‐posterior direction. Results Twenty patients were included. Nine patients were FJSA positive, all of whom had synovitis, bone marrow enhancement of the facet joints, and epidural phlegmon. No patients had epidural abscess, but five patients had a paraspinal abscess. All nine patients demonstrated extensive paraspinal muscular enhancement. Eleven biopsy cases that were negative for FSJA were included. Their MRI findings demonstrated all with synovitis, six with bone marrow enhancement of the facet joints, six with epidural phlegmon, none with epidural abscess, and none with paraspinal abscess. Only one FJSA negative case had extensive paraspinal muscle enhancement. Conclusion The MRI appearance of FJSA has rarely been described in the literature; however, the diagnosis has a significant clinical impact. Facet enhancement with florid posterior paraspinal muscle enhancement should raise suspicion for FSJA.

ABSTRACT Background The relationship between height differences related to graft anatomy and physiological pressure indices in coronary bypass grafts has not been studied. We sought to study the impact of hydrostatic pressure on fractional flow reserve (FFR) in saphenous vein grafts (SVGs). Methods Included were 66 symptomatic patients (76 SVGs) with prior coronary artery bypass grafting who underwent coronary computed tomography angiography (CCTA) preceding invasive coronary angiography with FFR interrogation of ≥ 1 SVGs. The graft course and height excursion were reconstructed based on CCTA images. The impact of hydrostatic pressure on FFR (corrected FFR) was calculated by adding or subtracting 0.077 mmHg to the distal coronary pressure for every millimeter height difference in a supine position between the SVG ostium and the pressure wire tip position. Results The height difference (mm) between the SVG ostium and pressure wire tip position was largest for single SVGs to the circumflex artery (Cx; −55.1 ± 17.0), followed by sequential SVGs to the Cx (−51.8 ± 17.3) and the right coronary artery (RCA; −36.7 ± 21.6). The correlation between height difference and uncorrected FFR was −0.59 ( p < 0.001). Corrected FFR was lower as compared to uncorrected FFR in the overall cohort (0.86 ± 0.17 vs. 0.88 ± 0.18), in single SVGs to Cx (0.85 ± 0.17 vs. 0.90 ± 0.18), and in sequential SVGs to Cx (0.92 ± 0.14 vs. 0.96 ± 0.15) and RCA (0.82 ± 0.17 vs. 0.85 ± 0.21) ( p < 0.001 for all). Conclusions Hydrostatic pressure related to height differences along the course anatomy of SVGs can impact FFR measurements, with corrected FFR being significantly lower in SVGs to the Cx and sequential SVGs to the RCA.

Pediatric regional anesthesia offers significant benefits, yet its adoption faces barriers, including perceived overcomplexity. This study aimed to identify and establish a set of core, high-value, low-complexity nerve blocks to improve perioperative pain management in pediatric patients. A four-round modified Delphi consensus study was conducted with an international panel of pediatric and regional anesthesia experts. An initial long list of regional techniques was compiled by the Steering Committee and refined through iterative input. Panelists rated each technique on a 10-point Likert scale for importance. Consensus was defined as ≥75% of panelists assigning a mean importance score of ≥8. Techniques receiving 50%–74% agreement were categorized as having strong agreement and considered for inclusion. The final selection was confirmed through a virtual roundtable discussion. Thirty-three experts representing 12 pediatric and regional societies participated. Consensus was reached on six regional techniques, with strong agreement (*) on two additional techniques, identifying eight core pediatric regional anesthesia blocks: supraclavicular brachial plexus block, rectus sheath block, transverse abdominis plane block*, suprainguinal fascia iliaca block*, femoral nerve block, adductor canal block, popliteal sciatic nerve block, and landmark-based caudal block. This consensus-driven framework defines a core set of pediatric regional anesthesia techniques that balance clinical effectiveness, feasibility, and accessibility. These findings provide a practical entry point for practitioners looking to incorporate pediatric regional anesthesia into their practice, regardless of prior experience. Future efforts should focus on standardized training, implementation research, and policy initiatives to support widespread adoption and improve perioperative pain management in children globally.