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Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Kiel Institute for the World Economy, Kiel, Germany
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Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, Tehran, Iran
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Background
We aimed to document the current state of exposure to low bone mineral density (BMD) and trends in attributable burdens between 2000 and 2019 globally and in different World Health Organization (WHO) regions using the Global Burden of Disease (GBD) study 2019.
Methods
We reviewed the sex-region-specific summary exposure value (SEV) of low BMD and the all-ages numbers and age-standardized rates of disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), and deaths attributed to low BMD. We compared different WHO regions (Africa, the Eastern Mediterranean Region, Europe, Region of the Americas, Southeast Asia, and Western Pacific), age categories, and sexes according to the estimates of the GBD 2019 report.
Results
The global age-standardized SEV of low BMD is estimated to be 20.7% in women and 11.3% in men in 2019. Among the WHO regions, Africa had the highest age-standardized SEV of low BMD in women (28.8% (95% uncertainty interval 22.0–36.3)) and men (16.8% (11.5–23.8)). The lowest SEV was observed in Europe in both women (14.7% (9.9–21.0)) and men (8.0% (4.3–13.4)). An improving trend in the global rate of DALY, death, and YLL was observed during 2000–2019 (−5.7%, −4.7%, and −11.9% change, respectively); however, the absolute numbers increased with the highest increase observed in global YLD (70.9%) and death numbers (67.6%). Southeast Asia Region had the highest age-standardized rates of DALY (303.4 (249.2–357.2)), death (10.6 (8.5–12.3)), YLD (133.5 (96.9–177.3)), and YLL (170.0 (139–197.7)).
Conclusions
Overall, the highest-burden attributed to low BMD was observed in the Southeast Asia Region. Knowledge of the SEV of low BMD and the attributed burden can increase the awareness of healthcare decision-makers to adopt appropriate strategies for early screening, and also strategies to prevent falls and fragility fractures and their consequent morbidity and mortality.
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Objective
Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease.
Design
Retrospective cohort study from a single institution.
Methods
We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease.
Results
We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021.
Conclusion
Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.
Significance statement
Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.
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Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.
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Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK
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Multimodality cancer therapy has led to remarkable improvements in survival of childhood and young adult cancer, with survival rates exceeding 85%. Such remission rates come with their own adverse sequelea or ‘late effects’. Although the cause of these late effects is multi-factorial, radiation-related adverse effects are one of the most prevalent. Hypopituitarism is a recognised complication of irradiation of brain tumours distant to the hypothalamo-pituitary (HP) axis when the axis is included within the exposed field. Much of the data concerning the development of hypopituitarism, however, relate to early forms of photon-based radiotherapy. In this narrative review, we discuss advances in individual radiotherapy techniques currently used in treating brain tumours and their theoretical benefits based primarily on dosimetric studies. Increasingly precise radiation techniques, including advances in the delivery of photons (i.e. intensity-modulated radiotherapy) and proton beam therapy, are now available options. The premise behind these newer techniques is to reduce the dose and volume of normal tissue irradiated whilst maintaining an effective radiation dose to target tissue. When treating brain tumours distant to the HP axis the expectation, based upon dosimetric studies, is that newer forms of radiotherapy will less frequently involve the HP axis in the exposed field, and where incorporated within the field it will be exposed to a lower radiotherapy dosage. Intuitively the dosimetric studies should translate into significant reductions in the prevalence of HP dysfunction. These data are promising; however, to date there are minimal robust clinical data to determine if the theoretical benefits of these newer techniques on HP dysfunction is to be realised.
Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Objective
To assess the long-term efficacy and safety of microwave ablation (MWA) in treating low-risk papillary thyroid microcarcinomas (PTMC) and to identify predictive factors for the postoperative local tumor progression of PTMC.
Methods
A total of 154 low-risk PTMC patients treated with MWA who were followed up for at least 3 months were retrospectively recruited. Ultrasonography was performed after MWA to assess the local tumor progression. Adverse events associated with MWA were recorded. The ablated volume (Va) and initial ablation ratio (IAR) were measured to assess their influences on the recurrence risk of PTMC.
Results
The mean tumor volume of PTMC before MWA was 0.071 (0.039, 0.121) cm3, with a maximum diameter of 0.60 ± 0.18 cm. All PTMC patients were followed up for 6 (3, 18) months. Va increased immediately after MWA, then gradually decreased over time, till significantly smaller at 12 months than that before MWA (P < 0.05). The median volume reduction ratio at 24 months reached 100%, which was maintained during a 60-month follow-up. A total of 7 (4.55%) cases of local tumor progression were recorded during the follow-up. Kaplan–Meier survival analysis revealed that the rate of local tumor progression was significantly lower in PTMC patients with a maximum tumor diameter < 0.70 cm than in those with ≥0.70 cm (P = 0.031). A significant better prognosis was achieved in PTMC patients with IAR ≥ 15 than in those with IAR < 15 (P = 0.015). Sex, age (<55 years) and preoperative thyroid-stimulating hormone (>2.0 mU/L) of PTMC patients were not correlated with local tumor progression.
Conclusion
MWA is an effective therapeutic strategy for low-risk PTMC with high safety. The maximum tumor diameter and IAR are predictive factors for the local tumor progression of PTMC after MWA.
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The current study aims to assess the development of the knowledge generation program of the European Reference Network on Rare Endocrine Conditions (Endo-ERN) from its start in 2019 until December 2021, with special reference to webinars. We analyzed the number of webinars and live/postevent participants and whether participation and engagement of the attendees changed over time. A total of 30 (86%) self-prepared webinars comprising 300 h of knowledge and competence sharing were broadcasted (2019 – 3; 2020 – 13; 2021 – 14). A total of six webinars were broadcasted live prior to the coronavirus disease 2019 pandemic (https://endo-ern.eu/events/webinars/). The most active main thematic group (MTG) was MTG3 Genetic Disorders of Glucose and Insulin Homeostasis with eight (27%) webinars. Two (25%) MTGs fulfilled the goal to prepare at least two to three webinars per year. Patients were actively involved in 20% of the accounted webinars as both creators and presenters. The total number of live and postevent participants was 3023. The availability of the webinars after the live broadcast increased their outreach with a larger number of postevent viewers (n = 1629, 54%). Within the formal structured evaluation of the webinars, 40–85% of the participants replied on separate occasions and helped improve content. The free webinar access is among the perceived reasons for the rapidly increasing number of total hits to the Endo-ERN website. In conclusion, for its short existence, the Endo-ERN rapidly developed educational outreach, and further efforts to attract creators and learners are warranted.
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Objectives
The activation of immune cells plays a significant role in the progression of type 2 diabetes. This study aimed to investigate the potential role of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) in type 2 diabetes.
Methods
A total of 61 patients diagnosed with type 2 diabetes were recruited. Clinical characteristics were reviewed and peripheral blood samples were collected. We calculated the percentage of different cells. Frequencies of MDSC subsets refered to the percentage of G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DR-/low) in CD45 positive cells and the percentage of M-MDSCs (CD14+CD15-CD11b+CD33+HLA-DR-/low) in lymphocytes plus monocytes.
Results
Frequencies of programmed cell death ligand 1-positive granulocytic MDSCs (PD-L1+ G-MDSCs), programmed cell death ligand 2-positive monocytic MDSCs (PD-L2+ M-MDSCs), PD-L2+ G-MDSC, and programmed cell death protein 1-positive Tregs (PD-1+Tregs) were decreased in patients with type 2 diabetes. The frequency of PD-1+ Tregs was positively related to PD-L2+ M-MDSCs (r= 0.357, P = 0.009) and negatively related to HbA1c (r = -0.265, P = 0.042), fasting insulin level (r = −0.260, P = 0.047), and waist circumference (r = −0.373, P = 0.005).
Conclusions
Decreased PD-L2+ M-MDSCs and PD-1+ Tregs may promote effector T cell activation, leading to chronic low-grade inflammation in type 2 diabetes. These findings highlight the contribution of MDSCs and Tregs to the immunopathogenesis of type 2 diabetes and suggest their potential as targets for new therapeutic approaches.
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Background
Similar to the high-fat diet (HFD), the high-glycemic diet (HGD) contributes to the development and progression of type 2 diabetes mellitus (T2DM). However, the effect of HGD on gastrointestinal motility in T2DM and its underlying mechanisms remain unclear.
Methods
Thirty C57BL/6J mice were randomly designated into the normal-feeding diet (NFD) group, HFD group, and HGD group. The plasma glucose, plasma insulin, and gastrointestinal motility were examined. Meanwhile, the tension of isolated colonic smooth muscle rings was calculated, and the gut microbiota was analyzed by 16s rDNA high-throughput sequencing.
Result
After 16 weeks of HGD feeding, obesity, hyperglycemia, insulin resistance, and constipation were observed in HGD mice. Autonomic contraction frequency of the colonic neuromuscular system and electrical field stimulation-induced contractions were reduced in HGD mice. On the contrary, neuronal nitric oxide synthase activity and neuromuscular relaxation were found to be enhanced. Finally, gut microbiota analysis revealed that Rhodospirillaceae abundance significantly increased at the family level in HGD mice. At the genus level, the abundance of Insolitispirillum increased remarkably, whereas Turicibacter abundance decreased significantly in HGD mice.
Conclusion
HGD induced constipation in obese diabetic mice, which we speculated that it may be related to neuromuscular dysmotility and intestinal microbiota dysbiosis.
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Background
There is no consensus strategy for mineralocorticoid (MC) therapy titration in patients with primary adrenal insufficiency (PAI). We aim to measure serum fludrocortisone (sFC) and urine fludrocortisone (uFC) levels and to determine their utility, alongside clinical/biochemical variables and treatment adherence to guide MC replacement dose titration.
Methods
Multi-centre, observational, cross-sectional study on 41 patients with PAI on MC replacement therapy. sFC and uFC levels (measured by liquid chromatography-tandem mass spectrometry), plasma renin concentration (PRC), electrolytes (Na+, K+), mean arterial blood pressure (MAP), total daily glucocorticoid (dGC) and MC (dMC) dose, and assessment of treatment adherence were incorporated into statistical models.
Results
We observed a close relationship between sFC and uFC (r = 0.434, P = 0.005) and between sFC and the time from the last fludrocortisone dose (r = −0.355, P = 0.023). Total dMC dose was related to dGC dose (r = 0.556, P < 0.001), K+ (r = −0.388, P = 0.013) as well as sFC (r = 0.356, P = 0.022) and uFC (r = 0.531, P < 0.001). PRC was related to Na+ (r = 0.517, P < 0.001) and MAP (r = −0.427, P = 0.006), but not to MC dose, sFC or uFC. Regression analyses did not support a role for sFC, uFC or PRC measurements and confirmed K+ (B = −44.593, P = 0.005) as the most important variable to guide dMC titration. Of the patients, 32% were non-adherent with replacement therapy. When adherence was inserted into the regression model, it was the only factor affecting dMC.
Conclusions
sFC and uFC levels are not helpful in guiding dMC titration. Treatment adherence impacts on clinical variables used to assess MC replacement and should be included as part of routine care in patients with PAI.
University of Alcalá, Madrid, Spain
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Purpose
The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes.
Methods
This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8–5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels.
Results
The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups.
Conclusion
Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar.
