Citations

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

Abstract Background Acute hypoxemic and hypercapnic respiratory failure are among the most common reasons for ICU admission and need for invasive mechanical ventilation. Noninvasive respiratory support (NIRS) strategies—including high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP)—may prevent intubation, improve outcomes, and reduce ICU utilization. However, there is uncertainty regarding optimal patient and modality selection, resulting in variable implementation. There are no clinical practice guidelines comprehensively addressing the use of the different noninvasive respiratory support strategies across the spectrum of acute respiratory failure. Objective To update and develop new evidence-based clinical practice recommendations informing noninvasive respiratory support use, including HFNC, NIV and CPAP, in adults with acute respiratory failure. Methods A multidisciplinary panel used the GRADE approach to address four PICO questions related to the use of NIRS for hypoxemic and hypercapnic respiratory failure, preoxygenation for intubation, and post-extubation respiratory support. Recommendations were informed by several systematic reviews and network meta-analyses. Results The panel made a strong recommendation for HFNC and a conditional recommendation for NIV or CPAP for adults with acute hypoxemic respiratory failure with close monitoring for the need for escalation of respiratory support, based primarily on effects on need for intubation. For acute hypercapnic respiratory failure, the panel made a strong recommendation for NIV to reduce mortality and need for invasive mechanical ventilation, and a conditional recommendation for HFNC only in patients with less severe hypercapnia and with mild acidemia (eg, pH > 7.25), provided that close monitoring and prompt escalation to NIV are available. The panel made a strong recommendation for HFNC or NIV for preoxygenation prior to endotracheal intubation to prevent peri-intubation hypoxemia. The panel also issued a risk-based recommendation, suggesting HFNC for low-risk patients and NIV for high-risk patients to reduce the need for re-intubation following extubation after critical illness. Conclusions Noninvasive respiratory support strategies are effective in improving outcomes in a range of clinical scenarios. We provide evidence-based recommendations, which can be further informed by patient risk, institutional capacity, and interface tolerance.

Introduction Correct inhaler technique is of utmost importance in the optimal delivery of therapeutics utilized for respiratory illnesses. Previous research suggests that the ability of both patients and providers to correctly use these inhalers is sub-optimal and is associated with poorer patient outcomes. Further education about inhaler types and technique as part of residency education could serve to correct these trends. Methods Family medicine residents were taught correct inhaler technique with an inhaler training device (In-Check TM DIAL G16) using a didactic lecture with hands-on teaching exercise utilizing pharmacy interprofessional teaching. We assessed pre- and post-intervention comfort and knowledge of correct inhaler technique. Results Twenty of twenty-seven eligible family medicine residents attended an interdisciplinary workshop with clinical pharmacists with the purpose of improving inhaler technique comfort level and knowledge. A pre- and post-knowledge test and comfort questionnaire were provided to those participating. Comfort levels with prescribing different inhaler types increased after the intervention and knowledge of different inhalers improved. Conclusion Use of an inhaler training device coupled with an interdisciplinary lecture format improved provider knowledge of correct inhaler technique and comfort with prescribing inhalers.

Abstract As an intrinsically mechanosensitive organ, the lung experiences a range of mechanical forces. Chronic obstructive pulmonary disease (COPD) involves abnormal macroscopic cellular and extracellular matrix (ECM) changes that impact mechanical properties of the lung. Mechanosensitive Piezo1/2 channels are expressed in the lung including on airway smooth muscle cells (ASM) that mediate cellular responses to stretch and ECM biomechanics. The expression and roles of Piezos in COPD lung ASM are not known. We hypothesized that Piezo expression and activation are altered in COPD lung ASM influencing ECM regulation. Distribution of Piezo proteins in ASM and epithelium of small airways of COPD stage II and IV vs. non-COPD controls was assessed using immunohistochemistry and ImageJ (n=10-17/group). Isolated ASM cells from control (n=6) vs. COPD stage II and IV patients (n=3 each stage) were exposed to stretch or the Piezo1 agonist Yoda1 followed by measurement of ECM gene and protein expression. Less Piezo2 staining was observed in COPD IV patients compared to controls, with lesser area and intensity of staining in the epithelial layer, and lower intensity of staining in ASM and small airways as a whole. Fura-2-based imaging of ASM Ca 2+ showed lower influx after Yoda1 exposure in COPD II compared to control and COPD IV. Gene expression of Piezo1 increased upon stretching in controls but not in COPD ASM, while Piezo2 protein expression decreased with stretching in all groups. Yoda1 treatment resulted in decreased collagen1 , fibulin1 and periostin gene and collagen 1 and periostin protein expression in ASM. Overall, these results support a role for Piezo activation in abnormal ECM-ASM cell crosstalk in COPD.

Abstract The lung, one the largest branching organs in our body and vital for survival at first breath, is commonly known as the gas-exchange organ. Recent novel findings on lung sensing cells, molecules, and lung-brain crosstalk in the emerging discipline of interoception have highlighted the consideration of the lung as a sensory organ. Acknowledging the central importance of lung sensing to human health and disease, NHLBI convened a workshop to synthesize the past, current, and future of lung sensing research, with in-person presentations by ∼20 interdisciplinary experts and a large virtual audience. Here, we highlight the key topics discussed and summarize a blueprint for the future in this important field.

ABSTRACT Inpatient, acute care clinical pharmacists have contributed to many notable improvements in patient outcomes. Several studies have shown a reduction in mortality and other clinical markers when pharmacists are integrated within the care team. Economic analyses of inpatient clinical pharmacy services (CPS) generally demonstrate cost savings related to specific medication classes, prevention of adverse drug events, decreased length of stay, and decreased rehospitalization. Studies also show high satisfaction from other health care professionals, noting improvements in medication‐related patient safety. Finally, studies conducted in tertiary care hospital settings report high levels of patient satisfaction with CPS. As such, the ECHO framework, based on economic, clinical, and humanistic outcomes, is used herein to organize the summary of literature associated with CPS. Given the growing body of evidence, numerous health professional and government organizations recognize the role of pharmacists as an integral part of the inpatient team. Yet implementation of CPS has not been fully realized by hospitals and health systems. This paper briefly describes inpatient CPS, highlights many benefits of and endorsements for clinical pharmacist participation on interdisciplinary teams, and provides high‐level recommendations for health system administrators and the profession of pharmacy to further encourage broader integration of CPS into patient care teams. Effectively positioning inpatient clinical pharmacists as indispensable team members will require intentional work and strategic planning with a focus on high‐impact value, visibility, and leadership.

ABSTRACT Supplemental oxygen (hyperoxia), often provided to premature infants, can disrupt lung growth and contribute to development of neonatal and pediatric lung diseases, necessitating understanding of underlying mechanisms. We previously showed that even moderate hyperoxia (< 60% O 2 ) induces detrimental cellular senescence in 18–22 weeks human fetal airway smooth muscle (fASM), a key cell type in airway contractility and remodeling. In this study, we examined the ability of senotherapeutics Fucoidan and Dasatinib (D) + Quercetin (Q) (D + Q) to mitigate adverse effects of hyperoxia and assessed the preventive effect of mitochondrial antioxidants (MitoQ). fASM cells exposed to normoxia (21% O 2 ) or hyperoxia (50% O 2 ) were treated with Fucoidan [100 μg/mL], D + Q [250 nM + 375 nM] or MitoQ [100 nM] and assessed for senescence markers, senescence‐associated secretory profile (SASP), extracellular matrix (ECM) deposition, and cell viability. Our results showed that moderate hyperoxia increases senescence markers and SASP. Fucoidan decreased p21 expression and inhibited SASP release without inducing cell death, while D + Q decreased β‐galactosidase (β‐Gal) activity, p21 and plasminogen activator inhibitor‐1 (PAI‐1) expression, and caused cell death without affecting SASP in hyperoxia‐induced senescent fASM. MitoQ prevented increases in senescence markers and SASP in hyperoxia‐exposed fASM. These findings demonstrate distinct and viable strategies to counter hyperoxia‐induced fASM senescence. Fucoidan (senomorphic), D + Q (senolytic), and MitoQ (prophylactic antioxidant) represent promising, mechanistically different approaches to alleviate detrimental effects of moderate hyperoxia in developing airways towards limiting perinatal lung disease.

Abstract Background: Despite efficacy in metastatic clear cell renal cell carcinoma (ccRCC), immunotherapy currently has no role in the neoadjuvant setting. Suppressive tumor-associated macrophages (TAMs) are known to mediate resistance to immune checkpoint blockade (ICB) in ccRCC. In preclinical studies, IL-1β blockade reprograms TAMs toward an anti-tumor phenotype and promotes T cell activation, creating a tumor microenvironment (TME) more sensitive to ICB. To test this in patients, we conducted a correlative-rich neoadjuvant trial of IL-1β + PD-1 inhibition in localized ccRCC. Methods: SPARC-1 is a single-center, phase 1b study assessing the safety and feasibility of neoadjuvant canakinumab (αIL-1β) and spartalizumab (αPD-1) in patients with localized ccRCC (T1b-T4NanyM0 or TanyN1M0). All patients received 2 doses of canakinumab (300mg IV, Q4w) and spartalizumab (400mg IV, Q4w), 6 weeks (±7 days) prior to nephrectomy. The primary endpoint was safety and feasibility. Key secondary and exploratory endpoints included 12-month metastasis-free survival rate, pathologic response rate, and quantification of immune cell infiltration. To characterize immunologic reprogramming, fresh tumor specimens were collected at nephrectomy for single-cell RNA sequencing (scRNAseq) and multiparametric flow cytometry. Tissue from a treatment naïve cohort was collected for comparative analysis (n=16). Results: From August 15th, 2018, to January 30th, 2025, 14 patients were enrolled. There were no severe treatment-related adverse events (Grade ≥ 3) attributed to canakinumab or spartalizumab. At a median follow-up of 12.0 months (range, 6.3-12.0 months), the 12-month metastasis-free survival was 100%. Based on the ASSURE nomogram, the mean predicted 12-month recurrence risk was 16.7% (range, 4.7-46.5%). ScRNAseq revealed that treatment with αIL-1β + αPD-1 increased the frequency of TREM2+APOE+ TAMs (p=0.035), a population typically associated with immune suppression. However, these TAMs exhibited a phenotypic shift toward a less immunosuppressive state, with reduced IL-1β expression and increased CXCL9:SPP1 ratio, consistent with anti-tumor TAM polarization. Immune profiling revealed an increased CD8/CD4 T cell ratio (p=0.042) with modest enrichment of activated CD8+ T cells after treatment, supporting a more pro-inflammatory TME. Conclusions: The neoadjuvant combination of canakinumab (αIL-1β) and spartalizumab (αPD-1) is well-tolerated, feasible, and demonstrated promising clinical activity with no progression of disease observed in a localized ccRCC population at high risk of recurrence. Correlative analyses demonstrated that combined IL-1β and PD-1 blockade reprograms immunosuppressive TAMs, providing evidence that dual IL-1β and PD-1 inhibition can overcome myeloid-driven resistance in ccRCC. Clinical Trial Information: NCT04028245 Citation Format: Patrick J. McCann, Aleksandar Obradovic, Casey R. Ager, David H. Aggen, Catherine S. Spina, Chelsea L. Rahiman, Kaitlyn R. Campbell, Caroline Laplaca, Peyton C. Johnston, Amanda Kim, Katherine Gomez, Kriti Bagri Manjrekar, Mark N. Stein, Charles G. Drake, Karie Runcie, Matthew Dallos. Neoadjuvant IL-1β and PD-1 inhibition in localized clear-cell renal cell carcinoma: Clinical and correlative analyses of the phase 1b SPARC-1 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT017.

ABSTRACT Background Journal clubs provide opportunities for discussion of new and evolving practices and technologies. Objective We sought to evaluate the utility and effectiveness of a monthly web‐based cosmetic dermatology journal club facilitated by faculty, residents, and medical students. Results From May 2025 to September 2025, 16 articles were discussed and 41 responses were recorded (response rate: 60%). Most respondents found the journal club was an appropriate length, engaging, and very useful. Relevance, frequency, and likelihood to participate in the future varied significantly by participant type. Medical students and residents collectively considered the journal club too infrequent ( p = 0.03) and reported it had less relevance to their practice ( p < 0.001). Conclusion A monthly web‐based cosmetic dermatology journal club was generally positively received by respondents.

Abstract Annual breast cancer screening is a critical piece of women’s health. While mammography remains the gold standard, increased breast density leads to decreased sensitivity, underscoring the need for more sensitive and accessible screening methods. Liquid-based biopsies for early breast cancer detection are emerging but currently remain out of reach for clinical use. Recent data on nucleotide assessment from plasma in breast cancer have been mixed with 87% sensitivity for late-stage disease (stage 3-4) but only 20% sensitivity for early-stage disease (stage 0-2). Proteomics is an exciting area for early cancer screening where improvements in sample preparation and equipment have enabled major advances in early cancer detection. This is particularly true for a deep proteome assay as proteins can be identified which are 8-9 orders of magnitude less abundant than the most common plasma proteins. This study evaluates the presence of breast cancer using label-free shotgun mass spectrometry-based proteomics on less than 1 ml of plasma from 1,259 women classified as either healthy or newly diagnosed treatment naïve breast cancer patients with a focus on early-stage disease. We trained using a cohort of 845 women, comprising of 466 healthy and 379 with breast cancer and validated on 397 women (195 healthy and 202 breast cancer) using a protein-based machine learning classifier to distinguish these groups. All plasma samples were processed in a blinded manner coupled with semi-quantitative, label-free mass spectrometry (MS)-based analysis. The median number of proteins detected per patient across breast cancer and healthy individuals was 7,064 and 7,054, respectively. The validation performance achieved 92.3% specificity for healthy controls and an overall sensitivity of 92.6% with an AUC of 0.975 (95% CI: 0.961-0.987) for breast cancer patients. Sensitivity broken down by clinical stage (0-IV), molecular subtypes (HR+/HER2+, HR-/HER2+, HR+/HER2-, and HR-/HER2-) and pathological subtypes (LCIS, DCIS, ILC, and IDC) were ≥85% and indistinguishable across all stages and subtypes. Gene set enrichment analyses (GSEA) identified pathways including epithelial-to-mesenchymal transition (EMT) and PI3K-AKT signaling as enriched in the breast cancer samples, highlighting that our test can identify cancer-related proteins in early-stage patients. Overall, we have developed a highly sensitive blood-based assay that utilizes deep proteomic profiling to identify distinctive cancer specific signatures in women who are undergoing screening for breast cancer. This work enables us to develop a protein-based classifier from plasma for early detection of breast cancer and enhances screening strategies for women with dense breasts who are at average or high-risk based on family history, specific genetic mutations such as BRCA1/2, race, or other factors. Citation Format: Alec Horrmann, Yash Travadi, Jacob Carey, Kevin Mallery, Ella Boytim, Grant Schaap, Carissa Rungkittikhun, Kaylee Kamalanathan, Nathaniel R. Bristow, Catalina Galeano-Garces, Adam Groth, Alexa R. Hesch, Pooja Advani, Justin Hwang, Badrinath R. Konety, Justin M. Drake. Deep plasma proteomics for early-stage breast cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4073.