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Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
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The global burden of controlling and managing diabetes mellitus (DM) is a significant challenge. Despite the advancements in conventional DM therapy, there remain hurdles to overcome, such as enhancing medication adherence and improving patient prognosis. Digital therapeutics (DTx), an innovative digital application, has been proposed to augment the traditional disease management workflow, particularly in managing chronic diseases like DM. Several studies have explored DTx, yielding promising results. However, certain concerns about this innovation persist. In this review, we aim to encapsulate the potential of DTx and its applications in DM management, thereby providing a comprehensive overview of this technique for public health policymakers.
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Objective: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations.
Methods: Patients with ROHHAD syndrome reported before and after 2019 were divided into Groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in Group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups.
Results: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among Groups 1–3, the rates of cardiovascular manifestations were NA vs. 12.8% vs. 81.2%; gastrointestinal disturbances were 11.4% vs. 8.5% vs. 62.5%; strabismus was 25.7% vs. 12.8% vs. 62.5%; sleep disturbance was NA vs. 6.4% vs. 50.0%; and abnormal pain threshold was NA vs. 10.6% vs. 25.0% (all p<0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (p<0.01).
Conclusions: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.
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Background
Epigenetics, which involves regulatory modifications that do not alter the DNA sequence itself, is crucial in the development and progression of thyroid cancer. This study aims to provide a comprehensive analysis of the epigenetic research landscape in thyroid cancer, highlighting current trends, major research areas, and potential future directions.
Methods
A bibliometric analysis was performed using data from the Web of Science Core Collection (WOSCC) up to 1 November 2023. Analytical tools such as VOSviewer, CiteSpace, and the R package ‘bibliometrix’ were employed for comprehensive data analysis and visualization. This process identified principal research themes, along with influential authors, institutions, and countries contributing to the field.
Results
The analysis reveals a marked increase in thyroid cancer epigenetics research over the past two decades. Emergent key themes include the exploration of molecular mechanisms and biomarkers, various subtypes of thyroid cancer, implications for therapeutic interventions, advancements in technologies and methodologies, and the scope of translational research. Research hotspots within these themes highlight intensive areas of study and the potential for significant breakthroughs.
Conclusion
This study presents an in-depth overview of the current state of epigenetics in thyroid cancer research. It underscores the potential of epigenetic strategies as viable therapeutic options and provides valuable insights for researchers and clinicians in advancing the understanding and treatment of this complex disease. Future research is vital to fully leverage the therapeutic possibilities offered by epigenetics in the management of thyroid cancer.
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Aim: To define functional and anatomical pituitary disease following ICI therapy and describe any change in pituitary function with time.
Methods: Retrospective observational audit of patients on ICI therapy in our centre between 2013 and 2023. We reviewed all patients on ICI therapy under the oncology department at University Hospital Plymouth, and identified individuals referred to endocrinology with suspected adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. Pituitary disease was evidenced by low ACTH, other pituitary dysfunction and/or abnormalities on pituitary imaging.
Results: 954 patients received ICI therapy during the study period, and 37 developed HPA axis dysfunction. Median interval of onset of symptoms was 4 months. There was no recovery in cortisol or ACTH for any individual on repeated testing. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target corticotrophs with no evidence of recovery. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, appearing to be a particular feature of immune mediated hypophysitis. These were confined to the anterior aspect of the pituitary as striations and were not visible on any scans performed more than three months after disease onset.
Conclusion: These data show that immune related (IR) hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and therefore cortisol production.
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Background: Bariatric surgery induces significant weight loss, increases insulin sensitivity and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement.
Methods: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using non-targeted metabolic liquid chromatography-mass spectrometry (LC-MS) method.
Results: During the 1, 3, and 6 months postoperative follow-up, the BMI, HOMA-IR, liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement and liver fat content reduction.
Conclusions: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.
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The elevated level of hepatic oxidative stress (OS) in polycystic ovary syndrome (PCOS) is one of the important causes of liver abnormalities. Therefore, decreasing the level of hepatic OS in PCOS is beneficial to reduce the risk of PCOS-related liver diseases. Melatonin (MT), recognized as a potent antioxidant. Nevertheless, the efficacy of MT in alleviating hepatic OS associated with PCOS is yet to be established, and the precise mechanisms through which MT exerts its antioxidant effects remain to be fully elucidated. The aim of this study was to explore the potential mechanism by which MT reduces hepatic OS in PCOS. First, we detected elevated OS levels in the PCOS samples. Subsequently, with MT pretreatment, we discovered that MT could significantly diminish the levels of OS, liver triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)，while concurrently ameliorating mitochondrial structural damage in PCOS liver. Furthermore, we identified elevated autophagy levels in the liver of PCOS rats and an inhibition of the Keap1-Nrf2 pathway. Through MT pretreatment, the expression of LC3 was significantly decreased, while the Keap1-Nrf2 pathway was activated. Our study showed that MT could affect the Nrf2 pathway dependent on the P62/LC3 autophagy pathway, thereby attenuating hepatic OS in PCOS. These findings offer novel insights and research avenues for the study of PCOS-related liver diseases.
Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland
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Search for other papers by Mari Minasyan in
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Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland
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Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Krakow, Poland
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Objective
Cushing’s syndrome (CS) is associated with an 18-fold greater risk of venous thromboembolism (VTE). We aimed to identify factors which provoke VTE among patients with CS and VTE and to describe the anticoagulant regimen used in these cases.
Methods
In this retrospective observational study, patients included in the European Registry on CS (ERCUSYN) in Krakow center, Poland, were followed for the occurrence of VTE and anticoagulant treatment. We identified factors provoking VTE according to the International Society of Thrombosis and Hemostasis (ISTH), along with factors included in the Padua score and CS-VTE score.
Results
Of the 128 patients followed for a median of 4.3 years, there were nine patients who experienced ten VTE episodes (prevalence of 7.8% and incidence of 13.4 per 1000 patient-years). All VTEs were classified as provoked according to the ISTH guidance, predominantly due to the transient major and minor (50% and 20%, respectively) factors, while they were less commonly due to persistent (30%) factors. In 2/9 patients, we could not identify any risk factor for VTE according to the Padua score, while in 2/6 patients according to the CS-VTE score. Patients were mostly anticoagulated with vitamin K antagonists (4/8 patients), followed by direct oral anticoagulants (3/8) and low-molecular-weight heparin (1/8). The median duration of anticoagulation was 2.75 years and exceeded beyond the primary treatment in 28% of episodes provoked by transient factors.
Conclusion
Further, multicenter studies are required to create a validated thrombotic risk score and guidelines regarding VTE treatment in CS patients.
Search for other papers by Waleed K W Al-Badri in
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Purpose
This review aims to discuss the psychological aspects of Graves’ ophthalmopathy (GO), estimate the prevalence of depression and anxiety disorders in GO, examine whether these psychiatric disorders are more prevalent in GO than in Graves’ disease (GD) without eye disease, and evaluate the main contributors for depression and anxiety in GO.
Methods
A review of the literature.
Results
Both depression and anxiety are associated with GO. The prevalence of depression and anxiety disorders specifically in GO patients was estimated at 18–33% and 26–41%, respectively. The reported prevalence in GD patients ranged from 9% to 70% for depression and from 18% to 88% for anxiety disorders. Significantly higher levels of depression and anxiety were found in GD patients compared with patients with non-autoimmune hyperthyroidism. Conflicting results have been reported regarding the association of antithyroid autoantibodies with depression and anxiety disorders. Serum thyroid hormone levels do not correlate with the severity of depression and anxiety. An improvement of psychiatric symptoms is observed in hyperthyroid patients after treatment of thyrotoxicosis. Moreover, depression and anxiety are significantly related to impaired quality of life (QoL) in GO. Exophthalmos and diplopia were not associated with depression nor anxiety, but orbital decompression and strabismus surgery do seem to improve QoL in GO patients.
Conclusions
The results of this review suggest that altered thyroid hormone levels and autoimmunity are prognostic factors for depression and anxiety in GO. With regard to the visual and disfiguring aspects of GO as contributing factors for depression and anxiety, no decisive conclusions can be made.
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Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumor in Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples during July 2021 to August 2022. 2337 (82%) of the cohort possess genetic alterations including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%) and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF positive papillary thyroid cancer (PTC) patients tend to have elder age, smaller tumor size, less vascular invasion, more frequent tumor multifocality and significantly higher cervical lymph node metastatic rate. Mutation at RET gene codon 918 and 634 is strongly correlated with medullary thyroid cancer (MTC), However it did not display more invasive clinical characteristics. TERT positive patients are more likely to have elder age, larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating poor prognosis. Patients with TERT, RET/PTC1 and CHEK2 mutation are more susceptible to lateral lymph node metastasis. In conclusion. NGS can be a useful tool which provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.
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Fanconi anemia (FA), dyskeratosis congenita-related telomere biology disorders (DC/TBD), and Diamond–Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) with high risks of bone marrow failure, leukemia, and solid tumors. Individuals with FA have reduced fertility. Previously, we showed low levels of anti-Müllerian hormone (AMH), a circulating marker of ovarian reserve, in females with IBMFS. In males, AMH may be a direct marker of Sertoli cell function and an indirect marker of spermatogenesis. In this study, we assessed serum AMH levels in pubertal and postpubertal males with FA, DC/TBD, or DBA and compared this with their unaffected male relatives and unrelated healthy male volunteers. Males with FA had significantly lower levels of AMH (median: 5 ng/mL, range: 1.18–6.75) compared with unaffected male relatives (median: 7.31 ng/mL, range: 3.46–18.82, P = 0.03) or healthy male volunteers (median: 7.66 ng/mL, range: 3.3–14.67, P = 0.008). Males with DC/TBD had lower levels of AMH (median: 3.76 ng/mL, range: 0–8.9) compared with unaffected relatives (median: 5.31 ng/mL, range: 1.2–17.77, P = 0.01) or healthy volunteers (median: 5.995 ng/mL, range: 1.57–14.67, P < 0.001). Males with DBA had similar levels of AMH (median: 3.46 ng/mL, range: 2.32–11.85) as unaffected relatives (median: 4.66 ng/mL, range: 0.09–13.51, P = 0.56) and healthy volunteers (median: 5.81 ng/mL, range: 1.57–14.67, P = 0.10). Our findings suggest a defect in the production of AMH in postpubertal males with FA and DC/TBD, similar to that observed in females. These findings warrant confirmation in larger prospective studies.
