Marloes Nies, Eus G J M Arts, Astrid E P Cantineau, and Thera P Links
Yejin Kim, Yoosoo Chang, Seungho Ryu, In Young Cho, Min-Jung Kwon, Sarah H Wild, and Christopher D Byrne
Despite the known benefit of vitamin D in reducing sarcopenia risk in older adults, its effect against muscle loss in the young population is unknown. We aimed to examine the association of serum 25-hydroxy vitamin D [25(OH)D] level and its changes over time with the risk of incident low muscle mass (LMM) in young and middle-aged adults.
This study is a cohort study.
The study included Korean adults (median age: 36.9 years) without LMM at baseline followed up for a median of 3.9 years (maximum: 7.3 years). LMM was defined as the appendicular skeletal muscle (ASM) mass by body weight (ASM/weight) of 1 s.d. below the sex-specific mean for the young reference group. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs.
Of the 192,908 individuals without LMM at baseline, 19,526 developed LMM. After adjusting for potential confounders, the multivariable-adjusted HRs (95% CIs) for incident LMM comparing 25(OH)D levels of 25–<50, 50–<75, and ≥75 nmol/L to 25(OH)D <25 nmol/L were 0.93 (0.90–0.97), 0.85 (0.81–0.89), and 0.77 (0.71–0.83), respectively. The inverse association of 25(OH)D with incident LMM was consistently observed in young (aged <40 years) and older individuals (aged ≥40 years). Individuals with increased 25(OH)D levels (<50–≥50 nmol/L) or persistently adequate 25(OH)D levels (≥50 nmol/L) between baseline and follow-up visit had a lower risk of incident LMM than those with persistently low 25(OH)D levels.
Maintaining sufficient serum 25(OH)D could prevent unfavourable changes in muscle mass in both young and middle-aged Korean adults.
Andreas Machens, Kerstin Lorenz, Frank Weber, and Henning Dralle
This study aimed to delineate the age-dependent clinical penetrance and expression of heterozygous rearranged during transfection (RET) missense mutations associated with multiple endocrine neoplasia 2A (MEN2A) according to parental inheritance.
This was an observational study of RET carriers operated for MEN2A-associated tumors between 1985 and 2021.
Kaplan−Meier time-to-event and multivariable Cox proportional hazards regression analyses were performed on node metastases from medullary thyroid cancer, pheochromocytoma, bilateral pheochromocytoma, and primary hyperparathyroidism.
Some 405 (70.1%) of 578 patients carrying heterozygous MEN2A RET missense mutations had information about the parental inheritance of the trait. On Kaplan−Meier analysis, offspring who inherited the trait from the father developed node metastases (P log-rank= 0.007), pheochromocytoma (P log-rank= 0.029), bilateral pheochromocytoma (P log-rank= 0.002), and primary hyperparathyroidism (P log-rank= 0.018) at a significantly younger age than offspring who inherited the trait from the mother. On multivariable Cox regression, controlling for index status, offspring sex, and (where feasible) mutational risk, parental inheritance was consistently associated with each MEN2A-associated tumor (hazard ratios (HR) = 1.7–1.8 for the earlier manifestations node metastases and pheochromocytoma vs HR of 2.9–3.4 for the late manifestations bilateral pheochromocytoma and primary hyperparathyroidism). Herein, node metastases were 3.1- and 1.7-fold more closely associated with mutational risk (HR of 5.3 for high and 2.9 for moderate-high risk mutations vs low-moderate risk mutations) than parental inheritance (HR = 1.7).
These findings illustrate the importance of considering not just mutational risk but also parental inheritance when it comes to personalization of screening for and early detection of the various components of MEN2A-associated tumors.
Evanthia Giannoula, Ioannis Iakovou, Luca Giovanella, and Alexis Vrachimis
Healthcare settings, including nuclear medicine (NM) departments, promptly adjusted their standard operating procedures to cope with the unprecedented crisis caused by coronavirus disease 19 (COVID-19) pandemic. Nuclear thyroidology has adopted changes and predicated on a careful risk–benefit analysis, in order to prevent a potential spread of the virus while being at the same time effective, safe and preserving their quality of essential services. Since most thyroid nodules (TNs) are benign, and malignant neoplasms are characterized by an indolent natural history, it is generally safe to delay diagnostic and therapeutic procedures. In this respect, the main adjustments that nuclear thyroidology has adopted are summarized into the following: general workplace adjustments including remote work for NM staff; postponing appointments for consultation, diagnostic and therapeutic purposes and rescheduling based on individualized risk stratification; telemedicine; preparation for possible issues on radiopharmaceuticals synthesis and delivery; preventing measures and protocols to minimize or avoid potential COVID-19 infection of patients and medical staff. This document should be considered as updated guidance on how clinical management of TNs and thyroid cancer has been altered, remodeled and adapted to the new circumstances in the COVID-19 era, based on the rapidly growing volume of scientific information regarding the new coronavirus.
Sophie H Bots, Rolf H H Groenwold, and Olaf M Dekkers
Electronic health record (EHR) data not only offer many exciting research opportunities but also come with their own inherent limitations. Researchers may not always realise the challenges associated with the use of EHR data for research, or the fact that using large datasets of ‘real-world data’ does not necessarily provide valuable real-world evidence. This article discusses some of the main differences between EHR data and data collected primarily for research purposes, and the challenges encountered when using EHR data for research. It also offers suggestions on how to deal with these challenges based on worked-out examples. It therefore serves as a quick guide for researchers interested in either reading or performing EHR-based research.
Nivedita Patni, Robert A Hegele, and Abhimanyu Garg
Frederic Castinetti, Jean Baptiste De Freminville, Carole Guerin, Erika Cornu, Gabrielle Sarlon, and Laurence Amar
The question of systematic use of a pharmacological treatment before surgery in patients diagnosed with pheochromocytoma and paraganglioma (PPGL) remains highly controversial. While recent guidelines suggest that this should be used in all patients, some experienced teams consider it unnecessary in some cases, provided the surgery is performed in a dedicated center that has expert endocrinologists, cardiologists, surgeons, and anesthetists. This controversy is aimed at shedding light on the potential benefits and risks of such a treatment, focusing specifically on alpha blockers which are considered as the first-line medical treatments in patients with PPGL. After discussing the rationale for alpha blockers, hemodynamic instability, tolerance and acute cardiac complications will then be discussed in the first part of the manuscript, defending a systematic use. The second section will focus on blood pressure control, tolerance of alpha blockers and also the management of normotensive PPGL, examining the daily risks of PPGL, and arguing against the systematic use of a preoperative pharmacological treatment before surgery. Finally we will discuss the concept of expert centers and define the patients in whom the risk/benefit profile would favor use of this preoperative treatment.
Mirko Parasiliti-Caprino, Fabio Bioletto, Chiara Lopez, Francesca Maletta, Marina Caputo, Valentina Gasco, Antonio La Grotta, Paolo Limone, Giorgio Borretta, Marco Volante, Mauro Papotti, Massimo Terzolo, Mario Morino, Barbara Pasini, Franco Veglio, Ezio Ghigo, Emanuela Arvat, and Mauro Maccario
Various features have been identified as predictors of relapse after complete resection of pheochromocytoma, but a comprehensive multivariable model for recurrence risk prediction is lacking. The aim of this study was to develop and internally validate an integrated predictive model for post-surgical recurrence of pheochromocytoma.
The present research retrospectively enrolled 177 patients affected by pheochromocytoma and submitted to radical surgery from 1990 to 2016, in nine referral centers for adrenal diseases. Cox regression analysis was adopted for model development, and a bootstrapping procedure was used for internal validation.
Variables independently associated with recurrence were tumor size (hazard ratio (HR): 1.01, 95% CI: 1.00–1.02), positive genetic testing (HR: 5.14, 95% CI: 2.10–12.55), age (HR: 0.97, 95% CI: 0.94–0.99), and Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) (HR: 1.16, 95% CI: 1.04–1.29). The predictive performance of the overall model, evaluated by Somers’ D, was equal to 0.594, and was significantly higher than the ones of any single predictor alone (P = 0.002 compared to tumor size; P = 0.004 compared to genetic testing; P = 0.048 compared to age; P = 0.006 compared to PASS). Internal validation by bootstrapping techniques estimated an optimistic bias of 6.3%, which reassured about a small tendency towards overfit.
We proposed a multivariable model for the prediction of post-surgical recurrence of pheochromocytoma, derived by the integration of genetic, histopathological, and clinical data. This predictive tool may be of value for a comprehensive tailoring of post-surgical follow-up in radically operated pheochromocytoma patients.
Evert F S van Velsen, Robin P Peeters, Merel T Stegenga, Uwe Mäder, Christoph Reiners, F J van Kemenade, Tessa M van Ginhoven, W Edward Visser, and Frederik Anton Verburg
The joint Union International Contre le Cancer and American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, Metastasis (TNM) staging system for differentiated thyroid cancer (DTC) involves a single age cutoff as a prognostic criterion. Because a single cutoff is a dichotomization of what might be a sliding scale, using multiple age cutoffs might result into a better stage definition. The aim of our study was to investigate if using a two-step age-based cutoff would improve the TNM staging system regarding disease-specific survival (DSS).
We retrospectively studied two cohorts of adult DTC patients from The Netherlands and Germany. DSS was analyzed for papillary (PTC) and follicular thyroid cancer (FTC) separately, investigating several two-step age-based cutoffs for those with distant metastases; below lower threshold classified as stage I, between lower and upper threshold as stage II, and above upper threshold as stage IV.
We included 3074 DTC patients (77% PTC). For PTC, an age cutoff of 45 with 50 years had the best statistical model performance, while this was 25 with 40 years for FTC. However, differences with the optimal single age cutoffs of 50 years for PTC and 40 years for FTC were small.
The optimal two-step age-based cutoff to predict DSS is 45 with 50 years for PTC and 25 with 40 years for FTC, rather than 55 years currently used for DTC. Although these two-step age-based cutoffs were marginally better from a statistical point of view, from a clinical point of view, the recently defined optimal single age cutoffs of 50 years for PTC and 40 years for FTC might be preferable.
Enora Le Roux, Agathe Turpin, Morgane Michel, Isabelle Tejedor, Florence Menesguen, Sabine Malivoir, Sandrine Bottius, Hélène Mellerio, Michel Polak, and Philippe Touraine
To evaluate the effect of a new care organization on multiple outcomes of transition success and its cost-effectiveness in patients with any endocrine or metabolic disease diagnosed during childhood and transferred to adult care.
Non-randomized controlled trial in a French university hospital.
Patients transferred to adult care during the control period (04/2014–08/2016) and the intervention period (09/2016–06/2018) were included. The intervention is based on case management involving liaising with pediatric services, personalizing care pathways, and liaising with structures outside hospital (general practitioner, educational and social sector). The primary endpoint was the percentage of patients lost to follow-up at 24 months post transfer. Other outcomes were collected from medical files, consultation software, and questionnaires. A cost analysis was performed.
Two hundred two patients were included (101 per period), the most represented pathologies were congenital and non-congenital hypopituitarism (respectively n = 34 (17%) and n = 45 (22%)) and thyroid diseases (n = 21, 10%). Patients were aged 22.5 in median at 24 months post transfer where 12 were lost to follow-up in the control group vs 9 with the intervention (P = 0.49). The percentage of honored consultation among those planned during 24 months was higher with intervention (P = 0.0065). Patient satisfaction, physician trust, and transfer delay did not differ between the groups. The incremental cost-effectiveness ratio was €179 per patient not lost to follow-up.
At 24 months post transfer, the rate of lost to follow-up did not differ significantly, but indicators of a steadier follow-up were increased and the intervention appeared to be cost-effective.