Patient perspectives and preferences for rehabilitation among people living with frailty and chronic kidney disease: a qualitative evaluation.

BACKGROUND: Understanding the patient perspective of frailty is critical to offering holistic patient-centred care. Rehabilitation strategies for patients with advanced chronic kidney disease (CKD) and frailty are limited in their ability to overcome patient-perceived barriers to participation, resulting in high rates of drop-out and non-adherence. The aim of this study was to explore patient perspectives and preferences regarding experiences with rehabilitation to inform a CKD/Frailty rehabilitation model. METHODS: This qualitative study involved two focus groups, six individual semi-structured interviews and three caregiver semi-structured interviews with lived experience of advanced kidney disease and frailty. Interviews were recorded, transcribed, and coded for meaningful concepts and analysed using inductive thematic analysis using constant comparative method of data analysis employing Social Cognitive Theory. RESULTS: Six major themes emerged including accommodating frailty is an act of resilience, exercise is endorsed for rehabilitation but existing programs have failed to meet end-users' needs. Rehabilitation goals were framed around return to normative behaviours and rehabilitation should have a social dimension, offering understanding for "people like us". Participants reported on barriers and disruptors to frailty rehabilitation in the CKD context. Participants valued peer-to-peer education, the camaraderie of socialisation and the benefit of feedback for maintaining motivation. Patients undertaking dialysis described the commodity of time and the burden of unresolved symptoms as barriers to participation. Participants reported difficulty envisioning strategies for frailty rehabilitation, maintaining a focus on the immediate and avoidance of future uncertainty. CONCLUSIONS: Frailty rehabilitation efforts in CKD should leverage shared experiences, address comorbidity and symptom burden and focus on goals with normative value.

ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells.

Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3+ T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models. Despite the broad expression of CD38 across human tissues, ISB 2001 demonstrated a reduced T cell activation profile in the absence of tumor cells when compared to TCEs targeting CD38 only. To determine an optimal first-in-human dose for the ongoing clinical trial ( NCT05862012 ), we developed an innovative quantitative systems pharmacology model leveraging preclinical data, using a minimum pharmacologically active dose approach, therefore reducing patient exposure to subefficacious doses of therapies.

Effect of Complete Transurethral Resection on Oncologic Outcomes After Radiation Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: To compare the oncologic outcomes of patients with nonmetastatic muscle-invasive bladder cancer (MIBC) undergoing complete versus incomplete transurethral tumor resection (TURBT) before radiation therapy. METHODS AND MATERIALS: Patients with nonmetastatic MIBC who underwent curative-intent radiation therapy between 2002 and 2018 at 10 Canadian institutions were retrospectively evaluated. Inverse probability of treatment weighting was performed using baseline characteristics. Differences in survival outcomes by complete and incomplete TURBT were analyzed. RESULTS: Of the 757 patients included, 66% (498) had documentation of a complete and 34% (259) an incomplete TURBT. Before adjustment, 121 (47%) and 45 (9%) patients who underwent incomplete and complete TURBT, respectively, were diagnosed with cT3-4 tumor (P <.001). After weight-adjustment, all baseline cohort characteristics were balanced (absolute standardized differences < 0.1). The adjusted median follow-up was 27 months. Adjusted survival analyses showed no significant difference in 5-year overall survival (48% vs 52%, 1.03 [0.82-1.29]; P = .8), cancer-specific survival (64% vs 61%, 0.93 [0.70-1.25]; P = .7), metastasis-free survival (43% vs 46%, 0.97 [0.79-1.19]; P = .8), and disease-free survival (32% vs 35%, 0.95 [0.79-1.15]; P = .7) between the 2 groups. CONCLUSIONS: Complete TURBT may be associated with clinical organ-confined disease. Extent of TURBT was not independently associated with oncologic outcomes in patients with MIBC treated with radiation therapy.

Single-photon induced instabilities in a cavity electromechanical device.

Cavity-electromechanical systems are extensively used for sensing and controlling the vibrations of mechanical resonators down to their quantum limit. The nonlinear radiation-pressure interaction in these systems could result in an unstable response of the mechanical resonator showing features such as frequency-combs, period-doubling bifurcations and chaos. However, due to weak light-matter interaction, typically these effects appear at very high driving strengths. By using polariton modes formed by a strongly coupled flux-tunable transmon and a microwave cavity, here we demonstrate an electromechanical device and achieve a single-photon coupling rate g 0 / 2 π of 160 kHz, which is nearly 4% of the mechanical frequency ωm. Due to large g0/ωm ratio, the device shows an unstable mechanical response resulting in frequency combs in sub-single photon limit. We systematically investigate the boundary of the unstable response and identify two important regimes governed by the optomechanical backaction and the nonlinearity of the electromagnetic mode. Such an improvement in the single-photon coupling rate and the observations of microwave frequency combs at single-photon levels may have applications in the quantum control of the motional states and critical parametric sensing. Our experiments strongly suggest the requirement of newer approaches to understand instabilities.

Long-Term Clinical, Radiological, and Mortality Outcomes Following Pneumonitis in Nonsmall Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Analysis.

AIMS: Despite known short-term mortality risk of immune checkpoint inhibitor (ICI) pneumonitis, its impact on 1-year mortality, long-term pulmonary function, symptom persistence, and radiological resolution remains unclear. METHODS: We retrospectively analyzed 71 nonsmall cell lung cancer (NSCLC) patients treated with anti-PD(L)1 monoclonal antibodies between 2018-2021, who developed pneumonitis. Clinical and demographic covariates were collected from electronic medical record. Cox regression assessed associations with mortality, while logistic regression evaluated associations with persistent symptoms, hypoxemia, and radiological resolution. RESULTS: Steroid-refractory pneumonitis (hazard ratio [HR] = 15.1, 95% confidence interval [95% CI]:3.9-57.8, P < .0001) was associated with higher 1-year mortality compared to steroid-responsive cases. However, steroid-resistant (odds ratio [OR] = 1.4, 95% CI: 0.4-5.1, P = .58) and steroid-dependent (OR = 0.4, 95% CI: 0.1-1.2, P = .08) pneumonitis were not. Nonadenocarcinoma histology (OR = 6.7, 95% CI: 1.6-46.6, P = .01), grade 3+ pneumonitis (OR = 4.6, 95% CI: 1.3-22.7, P = .03), and partial radiological resolution (OR = 6.3, 95% CI: 1.8-23.8, P = .004) were linked to increased pulmonary symptoms after pneumonitis resolution. Grade 3+ pneumonitis (OR = 8.1, 95% CI: 2.3-31.5, P = .001) and partial radiological resolution (OR = 5.45, 95% CI: 1.29-37.7, P = .03) associated with residual hypoxemia. Nonadenocarcinoma histology (OR = 3.6, 95% CI: 1.01-17.6, P = .06) and pretreatment ILAs (OR = 4.8, 95% CI: 1.14-33.09, P = .05) were associated with partial radiological resolution. CONCLUSIONS: Steroid refractory pneumonitis increases 1-year mortality in NSCLC patients. Pretreatment ILAs may signal predisposition to fibrosis-related outcomes, seen as partial resolution, which in turn is associated with postresolution symptoms and residual hypoxemia. These findings offer insights for identifying patients at risk of adverse outcomes post-pneumonitis resolution.

Radiation Recall Pneumonitis: Imaging Appearance and Differential Considerations.

Radiation recall pneumonitis is an inflammatory reaction of previously radiated lung parenchyma triggered by systemic pharmacological agents (such as chemotherapy and immunotherapy) or vaccination. Patients present with non-specific symptoms such as cough, shortness of breath, or hypoxia soon after the initiation of medication or vaccination. Careful assessment of the patient's history, including the thoracic radiation treatment plan and timing of the initiation of the triggering agent, in conjunction with CT findings, contribute to the diagnosis. Once a diagnosis is established, treatment includes cessation of the causative medication and/or initiation of steroid therapy. Differentiating this relatively rare entity from other common post-therapeutic complications in oncology patients, such as recurrent malignancy, infection, or medication-induced pneumonitis, is essential for guiding downstream clinical management.

Basaloid squamous cell carcinoma in the mandibular alveolus: A rare case report with differential diagnosis.

ABSTRACT: Basaloid squamous cell carcinoma (BSCC) is a distinct, high-grade variant of oral squamous cell carcinoma (OSCC) with a poor prognosis. In the head and neck region, the most common sites are the epiglottis, piriform sinus, and tongue base. Other less common sites include the floor of the mouth, oral mucosa, palate, tonsils, nasopharynx, and trachea. In the present report, the unusual case of a 69-year-old male is presented; the patient exhibited ulceroproliferative growth involving the lower alveolus. Incisional biopsy was done and the hematoxylin and eosin-stained sections revealed tumor islands with dysplastic oral epithelial cells invading the underlying connective tissue as islands, cords, and nests. The presence of palisading basaloid cells with a central area of comedo necrosis and keratin formation on the islands revealed the diagnosis of BSCC. Immunohistochemistry demonstrated positive staining for proliferative cell nuclear antigen (PCNA) and pan-cytokeratin. The patient is still under treatment and follow-up.

The Impact of Histologic Subtypes on Clinical Outcomes After Radiation-Based Therapy for Muscle-Invasive Bladder Cancer.

PURPOSE: Outcomes of radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC) with histologic subtypes of urothelial cancer (HS-UC) are lacking. Our objective was to compare survival outcomes of pure urothelial carcinoma (PUC) to HS-UC after RT. MATERIALS AND METHODS: A multicenter retrospective study of 864 patients with MIBC who underwent curative-intent RT to the bladder for MIBC (clinical T2-T4aN0-2M0) between 2001 and 2018 was conducted. Regression models were used to test the association between HS-UC and complete response (CR) and survival outcomes after RT. RESULTS: In total, 122 patients (14%) had HS-UC. Seventy-five (61%) had HS-UC with squamous and/or glandular differentiation. A CR was confirmed in 69% of patients with PUC and 63% with HS-UC. There were 207 (28%) and 31 (25%) patients who died of metastatic bladder cancer in the PUC and HS-UC groups, respectively. There were 361 (49%) and 58 (48%) patients who died of any cause in the PUC and HS-UC groups, respectively. Survival outcomes were not statistically different between the groups. The HS-UC status was not associated with survival outcomes in multivariable Cox regression analyses. CONCLUSIONS: In our study, HS-UC responded to RT with no significant difference in CR and survival outcomes compared to PUC. The presence of HS-UC in MIBC does not seem to confer resistance to RT, and patients should not be withheld from bladder preservation therapy options. Due to low numbers, definitive conclusions cannot be drawn for particular histologic subtypes.

Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis.

BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains. CONCLUSIONS: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

The Role of Chest Radiography in Lung Cancer.

Chest radiography is one of the most commonly performed imaging tests, and benefits include accessibility, speed, cost, and relatively low radiation exposure. Lung cancer is the third most common cancer in the United States and is responsible for the most cancer deaths. Knowledge of the role of chest radiography in assessing patients with lung cancer is important. This article discusses radiographic manifestations of lung cancer, the utility of chest radiography in lung cancer management, as well as the limitations of chest radiography and when computed tomography (CT) is indicated.

Imaging of Lung Cancer Staging: TNM 9 Updates.

Imaging plays a key role in clinical staging of lung cancer and guiding therapy. A thorough understanding of the staging system including the nomenclature and updates is necessary to tailor treatment plans and optimize patient care. The 9th edition of the Tumor, Node, Metastasis staging system for lung cancer has no changes for T classification and subdivides N2 and M1c categories. In nodal staging, N2 splits into N2a, ipsilateral mediastinal single station involvement and N2b, ipsilateral mediastinal multiple stations involvement. In the staging of multiple extrathoracic metastases, M1c splits into M1c1, multiple extrathoracic metastases in one organ system and M1c2, multiple extrathoracic metastases in multiple organ systems. Awareness of the proposed changes in TNM-9 staging classification is essential to provide methodical and accurate imaging interpretation.

Harnessing quantum light for microscopic biomechanical imaging of cells and tissues.

The biomechanical properties of cells and tissues play an important role in our fundamental understanding of the structures and functions of biological systems at both the cellular and subcellular levels. Recently, Brillouin microscopy, which offers a label-free spectroscopic means of assessing viscoelastic properties in vivo, has emerged as a powerful way to interrogate those properties on a microscopic level in living tissues. However, susceptibility to photo-damage and photo-bleaching, particularly when high-intensity laser beams are used to induce Brillouin scattering, poses a significant challenge. This article introduces a transformative approach designed to mitigate photo-damage in biological and biomedical studies, enabling non-destructive, label-free assessments of mechanical properties in live biological samples. By leveraging quantum-light-enhanced stimulated Brillouin scattering (SBS) imaging contrast, the signal-to-noise ratio is significantly elevated, thereby increasing sample viability and extending interrogation times without compromising the integrity of living samples. The tangible impact of this novel methodology is evidenced by a notable three-fold increase in sample viability observed after subjecting the samples to three hours of continuous squeezed-light illumination, surpassing the traditional coherent light-based approaches. The quantum-enhanced SBS imaging holds promise across diverse fields, such as cancer biology and neuroscience where preserving sample vitality is of paramount significance. By mitigating concerns regarding photo-damage and photo-bleaching associated with high-intensity lasers, this technological breakthrough expands our horizons for exploring the mechanical properties of live biological systems, paving the way for a new era of research and clinical applications.

Decoupling Fluorous Protein Coatings Yield Heat-Stable and Intrinsically Sterile Bioformulations.

Thermal inactivation is a major bottleneck to the scalable production, storage, and transportation of protein-based reagents and therapies. Failures in temperature control both compromise protein bioactivity and increase the risk of microorganismal contamination. Herein, we report the rational design of fluorochemical additives that promiscuously bind to and coat the surfaces of proteins to enable their stable dispersion within fluorous solvents. By replacing traditional aqueous liquids with fluorinated media, this strategy conformationally rigidifies proteins to preserve their structure and function at extreme temperatures (≥90 °C). We show that fluorous protein formulations resist contamination by bacterial, fungal, and viral pathogens, which require aqueous environments for survival, and display equivalent serum bioavailability to standard saline samples in animal models. Importantly, by designing dispersants that decouple from the protein surface in physiologic solutions, we deliver a fluorochemical formulation that does not alter the pharmacologic function or safety profile of the functionalized protein in vivo. As a result, this nonaqueous protein storage paradigm is poised to open technological opportunities in the design of shelf-stable protein reagents and biopharmaceuticals.

ACR Appropriateness Criteria® Sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Prevalence and prognosis of hypoxia-inducible factor-2α (HIF-2α) pathway gene mutations across advanced solid tumors.

INTRODUCTION: Hypoxia-inducible factor-2α (HIF-2α) modulates the hypoxic response pathway in tumors; however, mutations in pathways (including SDHA, SDHB, SDHC, SDHD, FH, and VHL genes) that are suspected to activate HIF-2α are poorly understood, with limited understanding of the prevalence and clinical prognosis. METHODS: This retrospective observational study used a de-identified nationwide (US-based) clinico-genomic database (CGDB) across 15 available tumor types. RESULTS: Among the 9467 adult patients with advanced/metastatic solid tumors included in the analysis, any mutation at the above-mentioned six genes was observed in 1.8% (95% CI: 1.5-2.1) of patients. The mutation prevalence ranged from 0.05% of SDHD to 0.93% of VHL. When further stratified by tumor type, the prevalence of gene mutation in each tumor type was well below 1%, except for VHL with 44% in renal cell carcinomas (RCC). Excluding RCC, the prevalence of any HIF-2α gene mutations in the study population was 0.9% (95% CI: 0.8-1.2). The median overall survival (OS) from 1 and 2 L therapy among patients with any HIF-2α gene mutation was 14.5 (95% CI: 11.5-24.2) and 9.3 (95% CI: 6.0-18.1) months, respectively, compared with 13.4 (95% CI: 12.9-13.9) and 9.8 (95% CI: 9.3-10.4) months among patients without HIF-2α gene mutations. DISCUSSION AND CONCLUSIONS: The prevalence of HIF-2α related gene mutations was generally low (<1%) across the 15 solid tumor types, except for VHL in RCC. No significant association between HIF-2α gene mutation status and OS was identified among patients evaluated in this study.

ACR Appropriateness Criteria® Sepsis

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Pericardial Recesses on Computed Tomography: Implications for the Pulmonologist.

The pericardium comprises a double-walled fibrous-serosal sac that encloses the heart. Reflections of the serosal layer form sinuses and recesses. With advances in multidetector computed tomography (CT) technology, pericardial recesses are frequently detected with thin-section CT. Knowledge of pericardial anatomy on imaging is crucial to avoid misinterpretation of fluid-filled pericardial sinuses and recesses as adenopathy/pericardial metastasis or aortic dissection, which can impact patient management and treatment decisions. The authors offer a comprehensive review of pericardial anatomy and its variations observed on CT, potential pitfalls in image interpretation, and implications for the pulmonologist with respect to unnecessary diagnostic procedures or interventions.

Drug-induced Lung Disease in the Oncology Patient: From Cytotoxic Agents to Immunotherapy.

Drug-induced lung disease is commonly encountered, especially in the oncology setting. Diagnosis is challenging because clinical and radiologic findings are nonspecific, often overlapping with other lung pathologies in these patients due to underlying neoplasia, infection, or other treatment effects such as radiotherapy. Furthermore, oncology patients often receive multiple antineoplastic agents concurrently, and virtually every agent has an association with lung injury. In this article, we will review a variety of antineoplastic agents that are associated with drug-induced injury and discuss incidence, their typical timing of onset, and imaging features.