Faculty Bibliography

OBJECTIVE:To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. SUMMARY BACKGROUND DATA/BACKGROUND:Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. METHODS:We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. RESULTS:We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

The early resuscitation of patients with mild to moderate non-exsanguinating trauma has shifted from the conventional use of one to two liters of crystalloids to the use of one to two units of PRBC. This evolution assumes that the transfusion of PRBC is superior to the administration of any volume of crystalloids because of the propensity of crystalloids to migrate from the intravascular to the interstitial space leading to organ dysfunction, organ failure, and worse outcomes. However, the premise of the fluid migration relies on Starling original model of fluid exchange between the hydrostatic and oncotic pressure without considering whether the endothelial surface glycocalyx (ESG) is affected by the degree of traumatic insult and by the duration and depth of hypotension. It fails to account for the changes that occur to the PRBC during storage from the standpoint of off-loading of oxygen and the ability to negotiate the microcirculation. This review explores the impact of the burden of trauma and hemorrhage on the ESG, the changes to the RBCs that occur during storage, particularly their diminished capacity to offload oxygen and to negotiate low-shear microvascular districts, leading to failure to improve oxygen consumption despite the increase in oxygen delivery. We argue that the recent trend toward early resuscitation with one to two units of PRBC rather that low-volume crystalloids, in patients with non-exsanguinating mild to moderate trauma lacks sufficient justification.

The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular resilience as a dynamic and multifaceted concept spanning molecular, cellular and systemic levels across an individual's lifespan. The workshop emphasized the need to expand the focus from solely understanding whether and how sleep and circadian rhythm disturbances contribute to disease, to also exploring how healthy sleep and aligned circadian rhythms can increase cardiovascular resilience. To develop a Roadmap towards this goal, workshop participants identified key knowledge gaps and research opportunities, including the need to integrate biological, behavioural, environmental and societal factors in sleep and circadian health with cardiovascular research to identify therapeutic targets. Proposed interventions encompass behavioural therapies, chronotherapy, lifestyle changes, organizational policies and public health initiatives aimed at improving sleep and circadian health for better cardiovascular outcomes. Future cross-disciplinary research and translation of discoveries into public health strategies and clinical practices could improve cardiovascular resilience across the lifespan in all populations.

AIMS/OBJECTIVE:To describe management of life with a left ventricular assist device (LVAD) by patients and caregivers and to determine the fit of self- and family management as a guiding concept in LVAD research. METHODS AND RESULTS/RESULTS:We applied dimensional analysis techniques to this concept analysis, beginning with a literature search (2010-25) of PubMed, CINAHL, Embase, PsycINFO, and Web of Science. Two reviewers screened and analysed 28 articles capturing perspectives on daily LVAD management among patients, caregivers, and healthcare professionals. Fourteen studies were qualitative, 12 were quantitative, and 2 were mixed methods. We identified five dimensions of patient and family management of LVAD therapy: patient facilitators and barriers; caregiver facilitators and barriers; processes of self- and family management; clinician facilitators and barriers/processes; and outcomes. These dimensions align with the concept of self- and family management and with core components of the Middle Range Theory of Self- and Family Management of Chronic Illness. CONCLUSION/CONCLUSIONS:This dimensional concept analysis advances understanding of managing life with an LVAD by clarifying the collaborative roles of patients, caregivers, LVAD coordinators, and other healthcare professionals. Our analysis supports the use of self- and family management as a guiding concept and the application of the Middle Range Theory of Self- and Family Management of Chronic Illness in LVAD research. A new conceptual definition of LVAD self- and family management reflects this theoretical grounding. Our work offers direction for future research, clinical practice, and education aimed at improving outcomes for patients and caregivers managing life with an LVAD.

IMPORTANCE/UNASSIGNED:Mental disorders have been associated with traditional cardiovascular risk factors that may mediate the risk of acute coronary syndrome (ACS). OBJECTIVE/UNASSIGNED:To estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders. DATA SOURCES/UNASSIGNED:MEDLINE, Embase, and PubMed were searched for studies between July 1, 2025, and date of database inception. STUDY SELECTION/UNASSIGNED:Study screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Association and/or risk of ACS. RESULTS/UNASSIGNED:Among 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22 048 504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.

Neoadjuvant therapy (NAT) is increasingly used for pancreatic ductal adenocarcinoma (PDAC); yet most patients only achieve partial response. Pathological treatment response grading focuses on assessing residual tumor burden, often overlooking changes in tumor microenvironment (TME). To address this gap, we compared tumor cells and TME of 13 NAT-naïve and 23 post-NAT PDACs using integrated spatial pathomics and transcriptomics, with validation in an independent single-cell spatial dataset. NAT significantly reduced tumor burden (14.7%-6.2%, p = 0.004), but systemic comparison of 13 cytomorphometric features of tumor cells alone did not reliably distinguish between naïve and NAT cases. In contrast, NAT profoundly remodeled TME by increasing cancer-associated fibroblast (CAF) and CD8⁺ T cell densities, promoting CD8⁺ T cell-tumor cell proximity and fibrosis, reducing tumor-associated neutrophils, and redistributing tertiary lymphoid structures (TLSs). Spatial transcriptomics shows NAT induced apoptosis, DNA-damage response, and AGC-kinase (S_TK_X) signaling in tumor cells, and upregulated complement pathway, p53 signaling, and cellular senescence program in TME. Cross-platform single-cell spatial analysis revealed decreased regulatory T cells (Treg) and a shift from myofibroblastic (mCAF) to inflammatory CAF (iCAF). Importantly, post-NAT patients with more fibrosis had longer overall survival (p = 0.02), and higher B-cell density showed a favorable trend (p = 0.06). Together, these results suggest that beyond tumor debulking, NAT induces a coordinated TME remodeling characterized by fibroblast reprogramming, matrix fibrosis, and immune spatial reorganization. Incorporating assessment of NAT-induced stromal and immune changes into TRG may improve prognostication and guide more precise therapy in post-NAT PDAC.

BACKGROUND:Although most adrenal incidentalomas are benign, many are identified by single-phase contrast-enhanced computed tomography, which is unreliable for excluding malignancy. Virtual noncontrast computed tomography is a newer modality with the potential to better characterize adrenal nodules. METHODS:Virtual noncontrast computed tomography of adrenal nodules with available reference standard of true noncontrast computed tomography were identified (2016-2024). Images were evaluated for nodule characteristics including Hounsfield unit attenuation and variability. Nodules were classified as benign (≤10 Hounsfield units) or indeterminate/suspicious (>10 Hounsfield units) by true noncontrast computed tomography. Hounsfield units were compared between virtual noncontrast computed tomography and true noncontrast computed tomography. Variability in attenuation measurements was compared by evaluating Hounsfield unit differences 1 slice up and down from the chosen mid-depth image. Receiver operating characteristic analysis was used to define optimal virtual noncontrast computed tomography accuracy thresholds. RESULTS:After excluding 5 adrenal nodules due to suboptimal imaging, 67 nodules were identified. Based on true noncontrast computed tomography Hounsfield units, 23 nodules (34.3%) were benign, and 44 (65.7%) were indeterminate/suspicious. Hounsfield unit measurements for each nodule exhibited wide variability by both virtual noncontrast computed tomography and true noncontrast computed tomography. Virtual noncontrast computed tomography and true noncontrast computed tomography were significantly correlated with moderate effect size (Pearson coefficient 0.69, P < .001). Conflicting impressions occurred for 6 nodules (9.0%). Overall, virtual noncontrast computed tomography exhibited outstanding discrimination between benign and indeterminate/suspicious nodules (area under the curve 0.94). Maintaining a threshold of ≤10 Hounsfield units achieved 93% sensitivity, 76% specificity, and 84% negative predictive value, whereas ≤7 Hounsfield units achieved 100% negative predictive value. The functional utility of virtual noncontrast computed tomography as a rule-out test applied to 16% of nodules. CONCLUSION/CONCLUSIONS:Despite wide variability in Hounsfield unit measurements, adrenal nodules are well defined by both virtual noncontrast computed tomography and true noncontrast computed tomography. Well-reconstructed virtual noncontrast computed tomography images can accurately rule out malignancy in selected patients, potentially obviating the need for additional imaging.