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.

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.

OBJECTIVE:Indeterminate lesions on prostate-specific membrane antigen (PSMA)-PET are challenging to address. We aimed to develop, implement, and evaluate a multidisciplinary consensus algorithm that integrates existing interpretation systems with multimodality imaging and clinicopathological information for interpreting indeterminate bone and lymph node lesions on PSMA-PET. MATERIALS AND METHODS/METHODS:This was a retrospective single-center study on a prospectively implemented algorithm. We included all consecutive prostate cancer patients whose PSMA-PET findings for indeterminate bone lesions or lymph nodes were discussed at a multidisciplinary tumor board (MDT) in 2024-2025. An algorithm determining the level of suspicion for metastasis was developed in a multidisciplinary fashion, incorporating lesion location, conventional imaging features, PSMA-PET characteristics, and clinicopathological information. The application of the algorithm and outcomes were documented, compared against a composite reference standard. Comparisons were made with PSMA-RADS and PROMISE V2 PSMA-expression scores. RESULTS:81 patients (median age 68, interquartile range 64-75) were included. Algorithm results were benign (48.1% [39/81]), equivocal (4.9% [4/81]), metastasis (40.7% [33/81]), and mixed (benign and metastatic lesions, 6.2% [5/81]). The algorithm was correct in 94.1% (64 of 68 patients with a sufficient reference standard). The algorithm was discordant with PSMA-RADS in 54.3% (44/81) and with PROMISE V2 PSMA-expression score in 71.6% (58/81). The frequency of equivocal lesions was lower using the algorithm (4.9% [4/81]) compared with PSMA-RADS (53.1% [43/81]) and PSMA-expression score (64.2% [52/81]). CONCLUSION/CONCLUSIONS:A multidisciplinary consensus algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET was developed and implemented. Integrating clinicopathological information and multimodality imaging in an MDT setting reduced equivocal interpretations. KEY POINTS/CONCLUSIONS:Question While prostate-specific membrane antigen (PSMA)-PET has become essential in the management of prostate cancer, indeterminate bone lesions and lymph nodes remain challenging to address. Findings A multidisciplinary algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging, reduced the frequency of equivocal interpretations. Clinical relevance An algorithm for interpreting indeterminate bone lesions and lymph nodes on PSMA-PET, incorporating clinicopathological information and multimodality imaging in a multidisciplinary tumor board setting, decreases the frequency of equivocal interpretations and can potentially help management decisions.

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.

Black women with estrogen receptor-positive, HER2-negative (ER + /HER2-) breast cancer experience higher rates of distant recurrence and worse survival outcomes compared to White women. This may be due not only to disparities in social determinants of health, but also differences in the tumor microenvironment (TME), including TMEM (Tumor Microenvironment of Metastasis) doorway score. TMEM doorways serve as portals for cancer cell hematogenous dissemination to distant sites. While higher TMEM doorway scores have been observed in Black (compared to White) patients with residual ER + /HER2- breast cancer after neoadjuvant chemotherapy, this has not been evaluated in treatment-naïve primary breast cancers. Here, we report on a multi-institutional study to evaluate TMEM doorway score in 418 treatment-naïve archived human breast cancer samples, including 265 patients with ER + /HER2-, 102 with triple negative (TNBC), and 51 with HER2-positive breast cancer. In addition to analyzing TMEM doorway scores by race across breast cancer subtypes, we examined their association with distant recurrence and assessed whether the effect of TMEM doorway scores on recurrence differed by race. Black patients had significantly higher TMEM doorway score than White patients in the overall study population (median 29.9 vs 17.9, p < 0.001), in the ER + /HER2- (median 25.0 vs 16.8, p < 0.001) and the HER2-positive subset (median 37.2 vs 12.9, p = 0.003), but not in TNBC (median 36.2 vs 36.3, p = 0.86). Racial differences in macrophage density mirrored racial differences in the TMEM doorway score. In multivariate models including age, body mass index, tumor size, grade, lymph node status, and chemotherapy treatment, neither Black race nor TMEM doorway density was associated with a higher distant recurrence risk alone. However, there was a statistically significant interaction between race and high TMEM doorway score with respect to distant recurrence risk in ER + /HER2- patients; Black patients with high TMEM doorway score were 4.6-fold (95% CI 1.28-22.82, p = 0.03) and 4.2-fold (95% CI 1.17 - 18.23, p = 0.04) more likely to have a distant recurrence at 5-years and 10-years, respectively, while White patients with high TMEM doorway scores did not (p = 0.21, p = 0.11). Our study reveals racial disparities in the TME of women with ER + /HER2- breast cancer, which may play a critical role in driving disparities in breast cancer outcomes.

Tibial tuberosity osteotomy (TTO) is a well-described treatment option for a broad range of patellofemoral joint disorders, including patellofemoral instability, focal chondral lesions of the patellofemoral joint, and patellofemoral arthritis. The purpose of this article is to review the indications and highlight the surgical technique for the more commonly performed TTO procedures and discuss outcomes, as well as surgical pearls for this technique.