A Novel and Generic Workflow of Indocyanine Green Perfusion Assessment Integrating Standardization and Quantification Towards Clinical Implementation

OBJECTIVE: This study aims to generate a reproducible and generalizable Workflow model of ICG-angiography integrating Standardization and Quantification (WISQ) that can be applied uniformly within the surgical innovation realm independent of the user. SUMMARY BACKGROUND DATA: Tissue perfusion based on indocyanine green (ICG)-angiography is a rapidly growing application in surgical innovation. Interpretation of have been subjective and error-prone due to the lack of a standardized and quantitative ICG-workflow and analytical methodology. There is a clinical need for a more generic, reproducible, and quantitative ICG perfusion model for objective assessment of tissue perfusion. METHODS: In this multicenter, proof-of-concept study, we present a generic and reproducible ICG-workflow integrating standardization and quantification for perfusion assessment. To evaluate our model's clinical feasibility and reproducibility, we assessed the viability of parathyroid glands after performing thyroidectomy. Biochemical hypoparathyroidism was used as the postoperative endpoint and its correlation with ICG quantification intraoperatively. Parathyroid gland are an ideal model as parathyroid function post-surgery is only affected by perfusion. RESULTS: We show that visual -subjective- interpretation of ICG-angiography by experienced surgeons on parathyroid perfusion cannot reliably predict organ function impairment postoperatively, emphasizing the importance of an ICG quantification model. WISQ was able to standardize and quantify ICG-angiography and provided a robust and reproducible perfusion curve analysis. A low ingress slope of the perfusion curve combined with a compromised egress slope was indicative for parathyroid organ dysfunction in 100% of the cases. CONCLUSION: WISQ needs prospective validation in larger series and may eventually support clinical decision-making to predict and prevent postoperative organ function impairment in a large and varied surgical population

Quality Indicators for the Diagnosis and Management of Primary Hyperparathyroidism

IMPORTANCE Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and there is low adherence to evidence-based treatment pathways. OBJECTIVE To develop quality indicators (QIs) to evaluate the diagnosis and treatment of pHPT that could measure, improve, and optimize quality of care and outcomes for patients with this disease. DESIGN, SETTING, AND PARTICIPANTS This quality improvement study used a guideline-based approach to develop QIs that were ranked by a Canadian 9-member expert panel of 3 endocrinologists, 3 otolaryngologists, and 3 endocrine surgeons. Data were analyzed between September 2020 and May 2021. MAIN OUTCOMES AND MEASURES Candidate indicators (CIs) were extracted from published primary hyperparathyroidism guidelines and summarized with supporting evidence. The 9-member expert panel rated each CI on the validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND-University of California, Los Angeles appropriateness methodology. All panelists were then asked to rank the top 5 QIs for primary, endocrine, and surgical care. RESULTS Forty QIs were identified and evaluated by the expert panel. After 2 rounds of evaluations and discussion, a total of 18 QIs were selected as appropriate measures of high-quality care. The top 5 QIs for primary, endocrine, and surgical care were selected following panelist rankings. CONCLUSIONS AND RELEVANCE This quality improvement study proposes 18 QIs for the diagnosis and management of pHPT. Furthermore, the top 5 QIs applicable to physicians commonly treating pHPT, including general physicians, internists, endocrinologists, otolaryngologists, and surgeons, are included. These QIs not only assess the quality of care to guide the process of improvement, but also can assess the implementation of evidence-based guideline recommendations. Using these indicators in clinical practice and health system registries can improve quality and cost-effectiveness of care for patients with pHPT

Interactive Effects of Racial Identity and Repetitive Head Impacts on Cognitive Function, Structural MRI-Derived Volumetric Measures, and Cerebrospinal Fluid Tau and A beta

Background: Factors of increased prevalence among individuals with Black racial identity (e.g., cardiovascular disease, CVD) may influence the association between exposure to repetitive head impacts (RHI) from American football and later-life neurological outcomes. Here, we tested the interaction between racial identity and RHI on neurobehavioral outcomes, brain volumetric measures, and cerebrospinal fluid (CSF) total tau (t-tau), phosphorylated tau (p-tau181), and Aβ1–42 in symptomatic former National Football League (NFL) players. Methods: 68 symptomatic male former NFL players (ages 40–69; n = 27 Black, n = 41 White) underwent neuropsychological testing, structural MRI, and lumbar puncture. FreeSurfer derived estimated intracranial volume (eICV), gray matter volume (GMV), white matter volume (WMV), subcortical GMV, hippocampal volume, and white matter (WM) hypointensities. Multivariate generalized linear models examined the main effects of racial identity and its interaction with a cumulative head impact index (CHII) on all outcomes. Age, years of education, Wide Range Achievement Test, Fourth Edition (WRAT-4) scores, CVD risk factors, and APOEε4 were included as covariates; eICV was included for MRI models. P-values were false discovery rate adjusted. Results: Compared to White former NFL players, Black participants were 4 years younger (p = 0.04), had lower WRAT-4 scores (mean difference = 8.03, p = 0.002), and a higher BMI (mean difference = 3.09, p = 0.01) and systolic blood pressure (mean difference = 8.15, p = 0.03). With regards to group differences on the basis of racial identity, compared to White former NFL players, Black participants had lower GMV (mean adjusted difference = 45649.00, p = 0.001), lower right hippocampal volume (mean adjusted difference = 271.96, p = 0.02), and higher p-tau181/t-tau ratio (mean adjusted difference = −0.25, p = 0.01). There was not a statistically significant association between the CHII with GMV, right hippocampal volume, or p-tau181/t-tau ratio. However, there was a statistically significant Race x CHII interaction for GMV (b = 2206.29, p = 0.001), right hippocampal volume (b = 12.07, p = 0.04), and p-tau181/t-tau ratio concentrations (b = −0.01, p = 0.004). Conclusion: Continued research on racial neurological disparities could provide insight into risk factors for long-term neurological disorders associated with American football play

Prognosis after surgery for multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: Functionality matters

Background: Metastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis. Methods: Patients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival. Results: Out of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%–76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%–91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47–6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22–7.33]) and World Health Organization grade 2 (2.95 [1.02–8.50]) were associated with liver metastases-free survival. Conclusion: Patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Autoinfarction of Giant Parathyroid Adenoma after Preoperative Withdrawal of Anticoagulants

A 71-year-old man with known history of atrial fibrillation (treated with routine rivaroxaban therapy) was found to have incidental biochemical elevated calcium and parathyroid hormone (PTH) levels. His physical examination demonstrated the presence of a palpable right neck mass. Subsequent imaging studies revealed a large parathyroid mass as well as multiple bone lesions, raising the suspicion of parathyroid carcinoma. The anticoagulant therapy was stopped 5 days prior to his elective surgery. The night before his elective surgery, he presented to the emergency room with profound hypocalcemia. The surgery was postponed and rescheduled after calcium correction. Intraoperative findings and detailed histopathological examination revealed an infarcted 4.0 cm parathyroid adenoma with cystic change. His bony changes were related to brown tumors associated with long-standing hyperparathyroidism. Autoinfarction of a large parathyroid adenoma causing severe hypocalcemia is a rare phenomenon and may be considered in patients with large parathyroid adenomas after withdrawal of anticoagulants

Preoperative Computed Tomography Changes Surgical Management for Clinically Low-Risk Well-Differentiated Thyroid Cancer

BACKGROUND: In the current guidelines for differentiated thyroid cancer (DTC), computed tomography (CT) of the neck has a limited role. The authors hypothesized that adding CT to the workup of clinically low-risk DTC size 4 cm or smaller changes the surgical management for a portion of patients due to detection of clinically significant lymph node metastases not located by ultrasound of the neck. METHODS: A prospective cohort of DTC patients at an academic referral center between 2012 and 2016 was reviewed. All the patients with fine-needle aspiration cytopathology results suspicious for malignancy or malignant tumor (Bethesda category 5 or 6, respectively) underwent CT before surgery. Clinically low-risk DTC patients were selected if they had a tumor diameter of 4 cm or less and no evidence for local invasion or suspicious lymph nodes seen on ultrasound. Outcomes focused on alteration of the surgical plan based on CT and correlation with pathology. RESULTS: The CT findings for 25 (22.5%) of 111 patients with clinically low-risk DTC led to a change in surgical management. Of these 25 patients, 16 (14.4% of the entire cohort) benefited due to the removal of clinically significant lymph node disease not seen on ultrasound. Categorization of the group that had a change in management showed that 6 (85.7%) of 7 lateral neck dissections and 10 (55.6%) of 18 central neck dissections (CND) harbored metastatic nodes larger than 2 mm. CONCLUSIONS: In the group with clinically low-risk DTC, CT changed surgical management for a substantial number of the patients with clinically significant nodal disease not detected by ultrasound. This highlights the fact that in certain practice settings, adding CT to the preoperative staging may be favorable for the detection of nodal metastasis

Strategic impact of a new academic endocrine surgery program.

BackgroundA minority of medical centers possess a dedicated endocrine surgery program. Here we assess the short-term impact of a new endocrine surgery program on institutional case volumes and financial endpoints.MethodsWe studied all endocrine procedures performed over a 5-year period spanning the inception of the endocrine surgery program at UCLA. Institutional and state-level data on patient geographic origin, discharges for endocrine diagnosis-related groups (DRGs), and hospital-side charges and costs were examined.ResultsTotal endocrine case volume increased 112% (264 to 559 cases annually) over the study period. The relative increase was greater for parathyroid (56 to 196, 250%, P < 0.0001) and adrenal (11 to 31, 181%, P = 0.06) procedures compared to thyroid procedures (317 to 442, 39%). The endocrine case volume of nonspecialist surgeons remained stable over the study period. Growth in referrals arose from previously unrepresented zip codes and was associated with an increase in the mean distance traveled for care (2006, 44 miles vs. 2009, 92 miles, P < 0.01). In each DRG, UCLA attained the top market position within one year of the program's inception, corresponding to an overall 27% increase in regional market share. Total hospital charges for endocrine DRGs rose 161% to $14.7 million annually, while the cost of parathyroid surgery fell 34% (P < 0.001).ConclusionsThe establishment of an academic endocrine surgery program can cause fundamental shifts in referral patterns within a competitive, densely populated metropolitan environment. Hospitals should consider the inclusion of an endocrine surgery program in strategic planning initiatives