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It is unclear whether parathyroidectomy guided by intraoperative parathormone (PTH) monitoring is predictive of operative success in patients with normohormonal hyperparathyroidism (nhHPT), a variant of primary hyperparathyroidism (pHPT) in which patients develop clinical manifestations similar to those of pHPT. This study examined intraoperative PTH monitoring in patients undergoing parathyroidectomy for nhHPT. We performed a retrospective review of prospectively collected data from adult (age > 18 yr) patients who underwent parathyroidectomy for pHPT at 1 of 2 North American medical centres (in Calgary, Alberta, Canada, or Miami, Florida, United States) between 2007 and 2015. In patients with nhHPT, we used the criterion of an intraoperative decrease of more than 50% in PTH after abnormal gland excision. We defined operative success as continuous eucalcemia more than 6 months after parathyroidectomy. Of 333 patients, 38 (11.4%) had nhHPT, with mean preoperative calcium and PTH levels of 2.7 mmol/L and 53 pg/dL, respectively. An intraoperative decrease of more than 50% in PTH level was seen in 27 patients (71.0%) with nhHPT and 265 patients (89.8%) with classic pHPT at 5 minutes (p < 0.001); the corresponding values at 20 minutes were 35 (92.1%) and 286 (96.9%). Although 5 patients (13.2%) with nhHPT did not reach this criterion until 20 minutes, the rate of operative success was still 97.0% at long-term follow-up (mean 13 mo, range 6–67 mo). Of the 38 patients, 3 (7.9%) did not have an intraoperative decrease of more than 50% in PTH level by 20 minutes. Two of the 3 achieved operative success and remained normocalemic, and 1 developed recurrent disease at 12 months. Parathyroidectomy guided by intraoperative PTH monitoring accurately predicted operative success in patients with nhHPT. Intraoperative PTH monitoring may also help identify multiglandular disease in patients with nhHPT, using criteria similar to those in classic pHPT, with comparable operative success. On ne sait pas si la parathyroïdectomie guidée par la surveillance peropératoire de la parathormone (PTH) permet de prédire le succès opératoire chez les patients atteints d’hyperparathyroïdie normo-hormonale (nhHPT), une variante de l’hyperparathyroïdie primaire (pHPT) qui entraîne chez les patients des manifestations cliniques similaires à celles de la pHPT. Cette étude a examiné la surveillance peropératoire de la PTH chez des patients subissant une parathyroïdectomie pour une nhHPT. Nous avons effectué une revue rétrospective des données recueillies prospectivement auprès de patients adultes (> 18 ans) ayant subi une parathyroïdectomie pour une pHPT à l’un ou l’autre de 2 centres médicaux nord-américains (à Calgary, en Alberta, au Canada, et à Miami, en Floride, aux États-Unis) entre 2007 et 2015. Chez les patients atteints de nhHPT, nous avons utilisé le critère d’une diminution peropératoire de plus de 50 % de la PTH après l’ablation de la glande anormale. Le critère de succès opératoire consistait en une eucalcémie continue plus de 6 mois après la parathyroïdectomie. Sur 333 patients, 38 (11,4 %) avaient une nhHPT, avec des taux moyens de calcium et de PTH préopératoires de 2,7 mmol/L et 53 pg/dL, respectivement. Une diminution peropératoire de plus de 50 % du niveau de PTH a été observée chez 27 patients (71,0 %) avec nhHPT et 265 patients (89.8 %) avec pHPT classique à 5 minutes (p < 0,001); les valeurs correspondantes à 20 minutes étaient 35 (92,1 %) et 286 (96,9 %). Bien que 5 patients (13,2 %) avec nhHPT n’aient pas atteint ce critère avant 20 minutes, le taux de succès opératoire était encore de 97,0 % lors du suivi à long terme (moyenne 13 mois, intervalle 6–67 mois). Sur les 38 patients, 3 (7,9 %) n’ont pas eu de diminution peropératoire de plus de 50 % du taux de PTH avant 20 minutes. Pour 2 de ces 3 patients, l’opération a réussi; ils sont demeurés normocalcémiques. L’autre patient a développé une maladie récurrente à 12 mois. La parathyroïdectomie guidée par la surveillance peropératoire de la PTH a permis de prédire avec précision le succès opératoire chez les patients atteints de nhHPT. La surveillance peropératoire de la PTH peut également aider à détecter une maladie multiglandulaire chez les patients atteints de nhHPT, par l’utilisation de critères similaires à ceux de la pHPT classique, avec succès opératoire comparable.

Abstract Transplant eligibility in patients with suspected or untreated malignancy presents a complex clinical dilemma. Transplant guidelines historically recommend a cancer-free interval of 2-to-5 years prior to solid organ transplantation to reduce the risk of recurrence under immunosuppression. However, these timelines are not always feasible. We present the case of a woman with end-stage lung disease found to have a thyroid nodule with intermediate-high risk of malignancy. Due to her severe respiratory illness, she was deemed unlikely to meet the recommended cancer-free interval. After multidisciplinary evaluation, the patient underwent bilateral lung transplantation prior to thyroidectomy. Concern for tumor progression under immunosuppression led to total thyroidectomy in the immediate postoperative period. This case highlights the need for flexible transplant evaluation pathways and presents a rare instance of non-emergent oncologic surgery performed in the immediate post-transplant period. This work contributes to a growing body of literature advocating for nuance in transplant oncology decision-making.

Focused parathyroidectomy (F-PTX) guided by intraoperative parathormone (ioPTH) monitoring may result in higher operative failure rates from missed multiglandular disease (MGD) in patients with sporadic primary hyperparathyroidism (spHPT) when ioPTH levels do not reach normal range. A retrospective review included 690 patients with spHPT who underwent F-PTX and ioPTH monitoring were divided into 2 groups: >50% ioPTH decrease to normal range, and >50% ioPTH decrease to above normal range. Operative success, recurrence, bilateral/unilateral neck exploration (BNE/UNE), MGD were evaluated. 533 patients demonstrated >50% ioPTH decrease to normal range, and 157 patients >50% ioPTH decrease to above normal range. There were no differences in operative success 99% vs. 97%, recurrence 2.5% vs. 5%, BNE 12% vs. 11%, UNE 4% vs. 5%, or MGD 4% vs. 4%, (p > 0.05) with 46 months mean follow-up. There were no differences in operative success, failure, BNE, UNE or MGD regardless of ioPTH criterion used for F-PTX. [Display omitted] •Primary sporadic hyperparathyroidism is a common cause of hypercalcemia.•Parathyroid surgery remains the only cure for primary sporadic hyperparathyroidism.•Miami criterion achieves operative success rates of 99% after parathyroidectomy.•Stricter criterion was not superior to Miami criterion to predict surgical success.

Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. A retrospective analysis of the Nationwide Inpatient Sample database (2006–2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P < 0.01). On multivariate analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59–176.6). Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy.

Protein aggregation plays a critical role in the pathogenesis of neurodegenerative diseases, and the mechanism of its progression is poorly understood. Here, we examine the structural and dynamic characteristics of transiently evolving protein aggregates under ambient conditions by directly probing protein surface water diffusivity, local protein segment dynamics, and interprotein packing as a function of aggregation time, along the third repeat domain and C terminus of Δtau187 spanning residues 255–441 of the longest isoform of human tau. These measurements were achieved with a set of highly sensitive magnetic resonance tools that rely on site-specific electron spin labeling of Δtau187. Within minutes of initiated aggregation, the majority of Δtau187 that is initially homogeneously hydrated undergoes structural transformations to form partially structured aggregation intermediates. This is reflected in the dispersion of surface water dynamics that is distinct around the third repeat domain, found to be embedded in an intertau interface, from that of the solvent-exposed C terminus. Over the course of hours and in a rate-limiting process, a majority of these aggregation intermediates proceed to convert into stable β-sheet structured species and maintain their stacking order without exchanging their subunits. The population of β-sheet structured species is >5% within 5 min of aggregation and gradually grows to 50–70% within the early stages of fibril formation, while they mostly anneal block-wisely to form elongated fibrils. Our findings suggest that the formation of dynamic aggregation intermediates constitutes a major event occurring in the earliest stages of tau aggregation that precedes, and likely facilitates, fibril formation and growth.

Background: Non-functional well-differentiated pancreatic neuroendocrine tumors (WD-PanNETs) are complex, heterogeneous malignancies with variable prognosis. Despite guideline recommendations, disparities in access to specialized care may impact survival. This study examines whether treatment facility type, geographic travel distance, and treatment modalities are associated with survival outcomes in patients diagnosed with WD-PanNETs. Results: Among 20,174 patients with WD-PanNETs, the median age was 62 years (IQR: 52–70), and 54% were men. The majority were treated at non-academic hospitals (76%), with 2.9% traveling >250 miles for care. Patients treated at non-academic hospitals (24%) had 50% lower 15-year survival rates compared to those treated at academic hospitals (58%) and integrated hospitals (56%) (p < 0.001). Patients traveling >250 miles had a 72% 15-year survival rate, compared to 43% for those traveling <12.5 miles (p < 0.001). In the context of facility-type and geographic distance, treatment at non-academic hospitals <250 miles was associated with a 21% higher mortality risk (HR 1.21, 95% CI 1.12–1.31, p < 0.001), and treatment at low-volume hospitals increased mortality risk by 25% (HR 1.25, 95% CI 1.14–1.37, p < 0.001). In contrast, primary tumor resection was associated with a 64% reduction in mortality risk (HR 0.36, 95% CI 0.33–0.38, p < 0.001), which remained significant at all disease stages. Conclusion: Treatment at academic or high-volume centers and longer travel distances were associated with improved OS in patients with WD-PanNETs. Primary tumor resection remains critical, while systemic therapies were primarily used in later-stage disease. These findings support policies that improve access to centralized, multidisciplinary care.

Objective To evaluate outcomes and predictors of survival of pediatric thyroid carcinoma, specifically papillary thyroid carcinoma. Methods SEER was searched for surgical pediatric cases (≤20 years old) of papillary thyroid carcinoma diagnosed between 1973 and 2011. Demographics, clinical characteristics, and survival outcomes were analyzed using standard statistical methods. All papillary types, including follicular variant, were included. Results A total of 2504 cases were identified. Overall incidence was 0.483/100,000 persons per year with a significant annual percent change (APC) in occurrence of 2.07 % from baseline ( P  < 0.05). Mean age at diagnosis was 16 years and highest incidence was found in white, female patients ages 15–19. Patients with tumor sizes <1 cm more likely received lobectomies/isthmusectomies versus subtotal/total thyroidectomies [OR = 3.03 (2.12, 4.32); P  < 0.001]. Patients with tumors ≥1 cm and lymph node-positive statuses [OR = 99.0 (12.5, 783); P  < 0.001] more likely underwent subtotal/total thyroidectomy compared to lobectomy/isthmusectomy. Tumors ≥1 cm were more likely lymph node-positive [OR = 39.4 (16.6, 93.7); p  < 0.001]. Mortality did not differ between procedures. Mean survival was 38.6 years and higher in those with regional disease. Disease-specific 30-year survival ranged from 99 to 100 %, regardless of tumor size or procedure. Lymph node sampling did not affect survival. Conclusions The incidence of pediatric papillary thyroid cancer is increasing. Females have a higher incidence, but similar survival to males. Tumors ≥1 cm were likely to be lymph node-positive. Although tumors ≥1 cm were more likely to be resected by subtotal/total thyroidectomy, survival was high and did not differ based on procedure.

Background Hungry bone syndrome (HBS) is a postoperative condition of severe hypocalcemia that can be seen in patients who have undergone parathyroidectomy (PTX) for secondary hyperparathyroidism (2HPT) of renal origin. This study examines HBS in patients after PTX for 2HPT. Methods Prospectively collected data was retrospectively reviewed in patients who underwent PTX for 2HPT of renal origin at a single institution. HBS was defined as the need for additional days of hospitalization or readmission for intravenous calcium supplementation due to clinical symptoms of hypocalcemia, including tingling, muscle spasms, and bone pain and/or immediate postoperative low serum calcium ≤7.5 mg/dl. Results Of 79 patients who underwent PTX for 2HPT, 27.8% ( n  = 22) experienced HBS. Young age (≤45 years, p  = 0.02) was the only preoperative variable that predicted HBS. Most patients developed HBS within 18 h after surgery and required a prolonged hospital stay (19/22) compared to those requiring hospital readmission within the first 7 days (3/22). Initial postoperative serum calcium levels within 18 h of surgery were significantly lower in those patients who developed HBS (7.1 vs. 8.3 mg/dl, p  = 0.001), and those patients also had a greater absolute decrease in serum calcium (2.8 vs. 3.5 mg/dl, p  = 0.04). Conclusion HBS develops in a significant proportion of patients generally within the first 18 h after subtotal PTX for 2HPT. The only identifiable preoperative risk factor for HBS was young age. Additionally, low initial calcium levels and greater absolute decrease in serum calcium may help identify those patients that will develop HBS requiring judicious calcium supplementation.

Reoperative parathyroidectomy (RPTX) for persistent or recurrent hyperparathyroidism is associated with a high rate of operative failure. The long-term effectiveness of RPTX using localization studies and intraoperative parathormone monitoring (IPM) was examined. Retrospective analysis of prospectively collected data from patients undergoing targeted RPTX with IPM for persistent or recurrent hyperparathyroidism was performed. Persistent hyperparathyroidism was defined as elevated calcium and parathormone (PTH) levels above normal range less than 6 months after parathyroidectomy. Recurrent hyperparathyroidism was defined as elevated calcium and PTH levels greater than 6 months after successful parathyroidectomy. Sensitivity and positive predictive value (PPV) for sestamibi, surgeon-performed ultrasound, intraoperative PTH dynamics, and surgical outcomes were evaluated. Of the 1,064 patients, 69 patients underwent 72 RPTXs with localizing studies and IPM. Sestamibi (n = 69) had a sensitivity of 74% and a PPV of 83%, whereas surgeon-performed ultrasound (n = 38) had a sensitivity of 55% and a PPV of 76%. IPM had a sensitivity of 100% and a PPV of 98%. An intraoperative PTH drop greater than or equal to 50% was predictive of operative success (P < .01). Overall, operative success and recurrence were 94% and 1.4%, with a mean patient follow-up of 59 ± 12.8 months. RPTX can be performed in a targeted approach using preoperative localization studies and IPM, leading to a low rate of complications and a high rate of long-term operative success.

Background Preoperative parathyroid localization studies, namely, sestamibi (MIBI) and surgeon-performed ultrasound (SUS), are commonly used for targeted parathyroidectomy (PTX) with intraoperative parathormone monitoring (IPM) in patients with primary hyperparathyroidism (pHPT). This study examined age-related variability in abnormal parathyroid gland localization for targeted PTX and the value of IPM across age groups. Methods A retrospective review examined prospectively collected data of 833 patients who underwent targeted PTX guided by IPM. The patients were stratified into three age groups as follows: younger [<47 years; mean −1 standard deviation (SD)], typical (47–73 years), and older (>73 years; mean +1 SD) based on an age distribution curve for pHPT. The accuracy, sensitivity, and positive predictive value (PPV) for MIBI, SUS, and IPM were analyzed and compared among age groups. Operative success was defined as eucalcemia for 6 months or longer after PTX, and operative failure was defined as elevated calcium and PTH levels within 6 months after PTX. Results Of the 833 patients, the youngest group had the highest accuracy and sensitivity for MIBI, SUS, and IPM compared with the older groups ( p  < 0.05). The accuracy and sensitivity of MIBI and SUS also decreased significantly with increased age ( p  < 0.05). Within all three age groups, IPM was consistently more accurate and sensitive than SUS or MIBI ( p  < 0.05). Conclusions Age can significantly affect the accuracy and sensitivity of MIBI and SUS in targeted PTX for patients with pHPT. Across all age groups, IPM remains more accurate than preoperative localization studies. For the elderly, in whom multiglandular disease appears increased, surgeons should have a lower threshold for conversion to bilateral neck exploration.