Citations

Background: Vascular endothelial growth factor inhibitors (VEGF-I) are frequently used for cancer treatment. VEGF-I can cause proteinuria and acute kidney injury (AKI) with thrombotic microangiopathy (TMA) as a commonly described pathology, but other glomerular pathologies are not well characterized. We aim to describe the clinical characteristics and glomerular lesions associated with VEFG-I in a single center cohort. Methods: We performed a retrospective chart review of patients treated with VEGF-I and underwent kidney biopsies from 2010 to 2022 at the Mayo Clinic, Rochester, MN. Biopsy findings were reviewed by our pathologists. Data on patients’ characteristics, clinical course, and outcomes were abstracted. Descriptive statistics were used to report relevant patient characteristics and findings. Results: From 2010 to 2022, 19 kidney biopsies were performed for kidney dysfunction in patients on VEGF-I. Eleven had complete data, with a median age of 62 years (interquartile range 58–66 years); renal cell carcinoma (RCC) was the most common cancer (4 of 11 patients). TMA was noted in 8 of the 11 biopsies, with proteinuria as the most frequent indication for biopsy in these cases. Three patients had findings other than TMA. One developed anti-phospholipase A2 receptor negative membranous nephropathy; VEGF-I and pembrolizumab were discontinued, and prednisone improved proteinuria. Another patient had known cryoglobulinemia with nephrotic range proteinuria which was exacerbated by VEGF-I peaking at 11 g/day. Despite stopping VEGF-I and treating with prednisone and rituximab, kidney dysfunction progressed to end stage kidney disease (ESKD). A third patient had IgA nephropathy with concurrent diabetic changes, but proteinuria progressed even after stopping VEGF-I. Conclusion: In this case-series of patients treated with VEGF-I undergoing kidney biopsy, we describe the pathological characteristics, clinical course, and outcomes of patients with pathologies other than TMA. Our study adds information to the sparse literature on patients with renal dysfunction after receiving VEGF-I.

AbstractThe American Academy of Otolaryngology–Head and Neck Surgery Foundation has published a supplement to this issue of Otolaryngology–Head and Neck Surgery featuring the updated “Clinical Practice Guideline: Adult Sinusitis”. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, an immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.

AbstractThe American Academy of Otolaryngology–Head and Neck Surgery Foundation has published the updated “Clinical Practice Guideline: Adult Sinusitis” as a supplement to this issue of Otolaryngology–Head and Neck Surgery. To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 14 developed recommendations address diagnostic accuracy for adult rhinosinusitis, the appropriate use of ancillary tests to confirm diagnosis and guide management (including radiography, nasal endoscopy, computed tomography, and testing for allergy and immune function), and the judicious use of systemic and topical therapy. Emphasis was also placed on identifying multiple chronic conditions that would modify management of rhinosinusitis, including asthma, cystic fibrosis, immunocompromised state, and ciliary dyskinesia. An updated guideline is needed as a result of new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group.MethodsThis executive summary describes the guideline developed using the 55‐page protocol published as the American Academy of Otolaryngology–Head and Neck Surgery Foundation's Clinical Practice Guideline Development Manual (3rd edition), which summarizes the methodology for assessments of current data, topic prioritization, development of key action statements, application of value judgements, and related procedures. The guideline update group represented the disciplines of otolaryngology–head and neck surgery, infectious disease, family medicine, allergy and immunology, advanced practice nursing, and a consumer advocate.Differences from Prior GuidelineThis clinical practice guideline is as an update, and replacement, for an earlier guideline published in 2015 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO‐HNSF).1 An update was planned for 5 years after the initial publication date and was further necessitated by new primary studies and systematic reviews that might suggest a need for modifying clinically important recommendations.2 Changes in content and methodology from the prior guideline include the following: New evidence from 14 guidelines, 194 systematic reviews, and 133 RCTs. Emphasis on patient education and counseling with new explanatory tables. Expanded action statement profiles to explicitly state quality improvement opportunities, confidence in the evidence, intentional vagueness, and differences of opinion. Enhanced external review process to include public comment and journal peer review. New algorithm to clarify decision making, watchful waiting, action statement relationships. Extension of watchful waiting (without antibiotic therapy) as an initial management strategy to all patients with uncomplicated acute bacterial rhinosinusitis (ABRS) regardless of severity, not just patients with “mild” illness (prior guideline). Clarified the recommended timeline for the diagnosis, conservative management and antibiotic treatment of ABRS. Change in recommendation to first‐line antibiotic therapy for ABRS amoxicillin, with or without clavulanate, from amoxicillin alone (prior guideline). Addition of aspirin exacerbated respiratory disease (AERD) as a chronic condition that modifies management of chronic rhinosinusitis (CRS). Three new key action statements on managing CRS that focus on the use of biologics (recommend against when patients do not have polyps and educate patients about them when they do) and a recommendation against the empiric use of antibiotics for CRS solely as a third‐party requirement for surgery or imaging.

Objectives: This study evaluates the efficacy of existing and new aerosol mitigation methods during nebulization (Neb) in combination with high-flow nasal cannula (HFNC) oxygen supplementation and non-invasive ventilation (NIV). Methods: We recorded fugitive aerosol particle concentrations over time and assessed the peak (P) and area (A) efficacy of active and passive mitigation methods, comparing them to a no-mitigation condition. Peak efficacy was measured by the reduction in maximum aerosol concentration, while area efficacy was quantified by the reduction of the area under the aerosol concentration–time curve. Results: For HFNC with Neb, we found that active mitigation using a mask with a biofilter and a fan (referred to as the aerosol barrier mask) significantly outperformed passive mitigation with a face mask. The peak and area efficacy for aerosol reduction were 99.0% and 96.4% for active mitigation and 35.9% and 7.6% for passive mitigation, respectively. For NIV with Neb, the active mitigation method, using a box with a biofilter and fan, also outperformed passive mitigation using only the box. The peak and area efficacy for aerosol reduction were 92.1% and 85.5% for active mitigation and 53.7.0% and 25.4% for passive mitigation, respectively. Conclusion: We concluded that active mitigation set up systems advantageous for effective reduction of airborne aerosols during aerosol generated procedures.

ABSTRACTObjectiveTo conduct an economic evaluation of a group mindfulness program compared to an education support program for breast cancer survivors (BCS).MethodsThe cost‐utility analysis (cost per quality‐adjusted life year [QALY]) was performed from a single‐center randomized controlled trial in the United States. Data from 181 BCS were included in the analysis (91 from the mindfulness‐based stress reduction for breast cancer, MBSR(BC) and 90 from the Breast Cancer Education Support, (BCES)). Analyses were conducted from two perspectives: societal and healthcare system. The EuroQol EQ‐5D‐5L was used to measure quality of life and the Client Service Receipt Inventory (CSRI) was used to measure health services utilization from baseline through 26 weeks. The impact of MBSR(BC) on health services utilization and costs was estimated with generalized linear models.ResultsIn the reference case analyses (societal perspective), the average total cost in the MBSR(BC) group was $5744 compared with $6140 in the BCES group. At the end of follow‐up, the MBSR(BC) group dominated BCES in terms of Incremental Cost Utility Ratio (ICUR), with MBSR(BC) providing an incremental cost of −$541 (95% CI: −$3400, $2318) and a 0.021 QALY (95% CI: −0.014, 0.055). Net monetary benefit (NMB) analysis showed that MBSR(BC) has a higher probability of achieving positive NMB across a range of possible societal willingness‐to‐pay for improving quality of life.ConclusionsOur findings suggest that MBSR(BC) is likely to be cost‐effective for breast cancer survivors over 6 months. Cost savings primarily resulted from reduced ER and hospital admissions and tests.

Abstract INTRODUCTION Monoclonal anti‐amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD). METHODS In the DIAN‐TU‐001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [ 11 C]‐Pittsburgh compound‐B (PiB) positron emission tomography (PET), [ 18 F]‐fluoro‐2‐deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI). RESULTS Gantenerumab significantly reduced PiB‐PET uptake overall and in most regions and showed no changes in FDG‐PET or MRI measures. Drug effects were associated with baseline PiB‐PET uptake, and the largest effects occurred in medial regions. DISCUSSION Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB‐PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design. Highlights Gantenerumab unevenly decreased Aβ burden as measured by PiB‐PET across brain regions. The strongest decrease in PiB‐PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG‐PET metabolism or MRI volumetrics after 4 years.

ABSTRACT Objectives Multicenter research of geriatric emergency department (GED) care remains limited. Our objectives were to: 1. Prospectively collect data prioritized by the Geriatric Emergency care Applied Research (GEAR) network, a transdisciplinary taskforce for GED care, and create a multicenter GED research repository of prospective and electronic health record (EHR) data, 2. Assess concordance between prospective and EHR data. Methods The GEAR Standardization Study (GEARSS) is a multicenter, prospective study of older emergency department (ED) patients (65+) focusing on the 4Ms of age‐friendly care (mobility, medication safety, mentation, what matters) and elder mistreatment. Demographic and clinical data were collected via interviews by trained research assistants (RA) on Days 0, 4, 30, and 90 and linked to EHR. Prevalence of chronic comorbidities and incident delirium were measured and reported using descriptive statistics. Prospective and EHR data concordance was assessed with Cohen's Kappa. Results 999 participants were recruited from 5 EDs (3/25/2021–6/30/2022) across 3 institutions: Grady Health System, Northwestern Memorial Hospital, and Yale New Haven Health. The cohort was 57.0% female, 55.2% White, 39.1% Black, and 3.4% Hispanic, and the mean age was 75.1 years. For rheumatologic disease, peptic ulcer disease, diabetes, renal disease, and cancer, prevalence differed between prospective and EHR data by > 10%. About two‐thirds of participants were at risk for falls. Concordance between prospective and EHR data was good for ethnicity ( K = 0.73); excellent for sex ( K = 1.00), age ( K = 1.00), and race ( K = 0.98); fair for disposition ( K = 0.53); slight for ED observation status ( K = 0.33) and dementia diagnosis ( K = 0.24); poor for delirium presence ( K = 0.07). Conclusion In GEARSS, demographic variables aligned strongly between prospective and EHR data, while diagnosis, disposition, and mentation factors did not. This multicenter data source provides preliminary findings for common geriatric syndromes and conditions. Choice of measures using these data should be driven by GED research questions.

Abstract Teclistamab is an anti-CD3-/B-cell maturation antigen (BCMA) bispecific antibody approved for use in relapsed/refractory multiple myeloma. We undertook a retrospective study of post-approval, real-world outcomes with teclistamab in the US Multiple Myeloma Immunotherapy Consortium. Among 509 patients, 89% would have been ineligible for the MajesTEC-1 trial, primarily due to prior BCMA-directed therapy, cytopenias, or diminished performance status. Cytokine release syndrome occurred in 54% (1.4% grade ≥3) and immune effector cell–associated neurotoxicity syndrome in 11% (2.2% grade ≥3), with no fatal events. Infections occurred in 42% and contributed to death in 5%. Partial response (PR) or better was achieved in 53% and very good PR or better in 45%. With 10.1 months of median follow-up, the estimated median progression-free survival (PFS) was 5.8 months and 12-month overall survival was 61%. Independent predictors of less than very good PR and shorter PFS included BCMA-directed chimeric antigen receptor T-cell therapy in the previous 9 months, high disease burden, lymphopenia, and elevated ferritin. Significance: T cell–engaging bispecific antibodies such as teclistamab represent an important new treatment modality for multiple myeloma and other blood cancers. This study evaluates the real-world safety and efficacy of teclistamab, including its activity in populations not represented in the initial phase I/II study, and identifies clinical variables associated with treatment response. See related commentary by Zweegman et al., p. 542