Endocrine and Metabolic Science最新文献

Objective

Pancreatic neuroendocrine neoplasms (pNENs) are histologically classified as well-differentiated, poorly-differentiated, or mixed neuroendocrine-non-neuroendocrine neoplasms. There are unresectable pNENs owing to metastases or invasion in not only functional pNENs but also non-functional. However, the exact origin of pNENs has not been elucidated. This study aims to characterize the molecular biology of pNENs based on clinical information and histopathological analysis and identify prognostic biomarkers.

Methods

We investigated the relationship between the biological characteristics and immunostaining of pathological tissues in 75 patients. Staining density was evaluated on a 4-point scale from 0 to 3, and the percentage of tumor cells was calculated and scored from 0 to 300 (H-score). We performed receiver operating characteristic (ROC) curve analysis of the H-score. Progression-free survival and overall survival analyses were performed based on the Kaplan–Meier curves.

Results

The H-score showed that patients who died of pNEN had high Ki-67 and low somatostatin receptor (SSTR) 2 levels, and those who relapsed had high Ki-67 and low SSTR5 levels. The ROC showed that the SSTR2 H-score > 80.25 was associated with lower mortality, which was further confirmed by Kaplan–Meier curves [hazard ratio (HR): 6.039, 95 % confidence interval (CI): 1.233–29.59, P = 0.0006). SSTR5 H-score > 93.9 had less recurrence, which was confirmed using Kaplan–Meier curves (HR: 3.321, 95 % CI: 1.426–7.734, P = 0.0336).

Conclusion

Ki-67 > 4.95 is associated with a significantly increased risk of death. Quantification of SSTR2 and SSTR5 immunostaining using the H-score may serve as prognostic markers.

Background

Papillary thyroid cancers are relatively common endocrine malignancies. Risks include obesity, smoking, family history, and radiation exposure. Estrogens may be associated with an increased risk; the implications for transgender women, who use estrogen for gender-affirming hormone therapy (GAHT), are unclear.

Cases

3 transgender female veterans seen at sites within our VA Health System were diagnosed with papillary thyroid cancer. All three had started some form of estrogenic GAHT prior to the diagnosis, between 3 months to 5 years earlier. One veteran had radiation exposure, one had a smoking history, and 2 were obese. 2 were treated with thyroidectomy, and one had a recurrence treated with RAI. Each veteran had started GAHT before coming to the VA, and one started without physician support.

Discussion

Thyroid cancer prevalence in the transgender female population is not yet well-established. These 3 transgender female veterans each had risk factors associated with cancer development. Based on limited existing data, it is conceivable but not clear that GAHT treatment could have impacted their course.

Conclusion

Further investigation of thyroid cancer among transgender women in general, and into the impact of GAHT on disease burden in particular, is needed. Clinicians should also be aware that patients may be receiving hormonal therapy from nontraditional sources with unforeseen and unknown associated risks.

Introduction

Haemoglobin A1c (HbA1c) levels might inaccurately represent long-term glycaemic control in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) owing to anaemia. Fructosamine, which reflects glycaemic control, remains unaffected by anaemia.

Material and methods

This study sought to assess whether fructosamine levels or fructosamine-albumin (FA) ratios could be biomarkers for glycaemic control in T2DM patients, with and without CKD. HbA1c and fructosamine levels were measured, and comparisons were made using the area under the curve and receiver operating characteristic curves. Youden's index was utilized to pinpoint the cut-off points. Predictive values for complications were also assessed.

Results

Our study underscores the close association between HbA1c and blood glucose concentrations among T2DM patients, regardless of kidney function status (r = 0.758). Conversely, fructosamine levels and FA ratios only displayed moderate correlations with FBG among those without CKD (r = 0.466 and r = 0.436, respectively). In a similar manner, the estimated blood glucose (eBG) levels derived from HbA1c were better than the ones from fructosamine levels and FA ratios in terms of comparation to actual fasting blood glucose (FBG) levels across various eGFR levels.

Conclusions

Our findings suggest that HbA1c remains a conventional gauge for glycaemic control among T2DM outpatients, regardless of CKD status. However, for short-term glycaemic monitoring in T2DM outpatients with CKD and low eGFR levels, fructosamine, and FA ratios emerge as potential biomarkers worthy of consideration.

Neck circumference is a low-cost and simple anthropometric measure that has been proven to accurately assess central obesity. However, evidence of its use and feasibility in low-resource settings is limited. We aimed to compare the utility of neck circumference with standard physical measures of obesity in northern Peru. This was a retrospective, cross-sectional study conducted among adults screened for metabolic syndrome. Body mass index, waist circumference, neck circumference, and additional measurements for metabolic syndrome were obtained. Assessments were performed following the WHO STEPS Surveillance Manual. Pearson correlation coefficients and multiple linear regression models were used to estimate the relationship of neck circumference to waist circumference and body mass index. Data from 250 participants showed a normal, homogeneous distribution in both men and women with respect to age and physical/biochemical measurements. The mean age was 53.6 years. A positive correlation of neck circumference with body mass index (r = 0.51 for women and 0.65 for men) and waist circumference (r = 0.6 for women and 0.74 for men) was observed. Multiple linear regression showed that a 1-cm increase in neck circumference increased body mass index by 0.72 kg/m² (p < 0.001) in men and 0.94 kg/m² (p < 0.001) in women, and waist circumference by 2.20 cm (p < 0.001) in men and 2.27 cm (p < 0.001) in women. Our findings suggest that neck circumference is a valid and reliable measure that will replace body mass index and waist circumference in Peruvian adults with central obesity; due to the strong correlation that exists between the NC and these anthropometric measurements, mainly because it is an easy, quick measurement and is less vulnerable to errors such as in the measurement of abdominal circumference or variabilities in weight.

Reproductive processes in fishes are regulated by the hypothalamic-pituitary-gonadal (HPG) axis, much like in tetrapods. Within this system, Gonadotropin-Releasing Hormone (GnRH) is released by the hypothalamus, binding to GnRH receptors in the pituitary gland and stimulating the secretion of gonadotropin hormones. The current study aimed to analyze the GnRH receptor in Oncorhynchus mykiss (rainbow trout) using a computational and structural biology approach. The GnRH receptor gene of O. mykiss comprises a nucleotide sequence of 1707 base pairs with an open reading frame of 1251 base pairs, which is responsible for encoding 416 amino acids. It was found that the GnRH receptor contains leucine (L) as the most abundant amino acid. The secondary structure revealed that alpha helices constitute the largest percentage (36 %) with 153 residues, followed by extended strands with 77 residues (17.51 %). The GnRH receptor contains 26 negatively charged and 37 positively charged amino acid residues. The highest hydrophilicity was observed for lysine (K) at position 310, with a value of −3.900, while the highest hydrophobicity was found for leucine (L) at position 290, with a value of 3.80. Molecular docking analysis showed that the most favorable binding energy was observed for Gestrinone (−7.8 kcal/mol). Gestrinone was found to form hydrogen bonds with MET160, LUE245, LUE62, TYR216, and GLN209 residues of GnRH. Moreover, molecular dynamics revealed that the complexes form robust and enduring connections, indicating their structural integrity throughout the simulation. The results of this study provide insights into the protein modeling, molecular docking, and virtual screening of antagonist ligands against the GnRH receptor. Additionally, they may significantly aid in the advancement and improvement of therapeutic strategies targeted at treating various fish reproductive dysfunctions.

Background

Atypical primary hyperparathyroidism (PHPT), which includes normocalcemic and normohormonal variants, can be a diagnostic challenge. We sought to create a machine learning model to predict the probability of a patient having atypical presentations of PHPT.

Methods

A model was constructed using logistic regression of PHPT patients and were compared to controls. Variables included sex, body mass index (BMI), calcium, PTH, 25-hydroxyvitamin D, phosphorus, chloride, sodium, alkaline phosphatase, and creatinine. The performance of the model was evaluated using the area under the curve (AUC).

Results

The study included 4987 controls and 433 patients with atypical PHPT. Calcium, PTH, vitamin D, phosphorus, BMI, and sex were found to significantly contribute to the performance of the model, achieving an AUC of 0.999. The sensitivity, specificity, positive and negative predictive values were 92.9 %, 99.7 %, 96.3 % and 99.4 %, respectively.

Conclusion

Machine learning can reliably aid in the recognition of PHPT in patients with atypical variants.

Clinical relevance

When evaluating patients with atypical variants of primary hyperparathyroidism, the clinician needs to be able to identify subtle relationships in the patient laboratory test to make the diagnosis. These relationships can be found with machine learning and incorporated to predictive models which can ease and improve the diagnosis.

Objective

Concerns exist about semaglutide, potentially worsening sight-threatening diabetic retinopathy (DR) in individuals with diabetes. This study aimed to explore the association between semaglutide and the risk of DR progression over three years in patients with type 2 diabetes (T2D). It is hypothesized that any observed deterioration in DR among T2D patients following semaglutide use would be temporary and unrelated to long-term progression.

Methods

Retrospective data analysis identified 4086 patients with T2D and DR by ICD-10 codes in a Retina only practice from January to June 2020. Use of semaglutide was found in 116 patients. Inclusion criteria included at least 1 year of semaglutide use and documentation of level of non-proliferative (NPDR) and proliferative (PDR) retinopathy, visual acuity (VA) and Central Subfield Thickness (CST).

Results

87 patients meeting the eligibility criteria, ranging in age from 38 to 84 years (mean age of 62.4 years), and having an average duration of semaglutide usage of approximately 2.9 years. Gender distribution included 58.6 % male and 41.4 % female patients, with 83.9 % Caucasian, 11.5 % Black, and 10.3 % Hispanic backgrounds. The baseline HbA1c level averaged 7.6 %, ranging from 5.9 % to 10.9 %, with a standard deviation of 1.1. The last self-reported HbA1c level averaged 7.4 %, ranging from 5.2 % to 14 %, with a standard deviation of 1.5. Baseline DR severity correlated with progression risk: 2.7 % for DRSS level ≤ 43, 28 % for levels 47/53, and 45 % for baseline PDR. Patients required an average of 12.6 intravitreal injections. Visual acuity remained stable for 72.4 % of patients, with 16.1 % experiencing a loss and 11.5 % achieving improvement.

Conclusion

Semaglutide use was not associated with increased risk of progression of DR, visual loss, or an increased number of intravitreal injections over a 3-year period of time.

The interaction of nutrients and bacterial-derived products and their enteroendocrine effects are still enigmatic. We used the human enteroendocrine tumour cell line P-STS isolated from the terminal ileum as cellular sentinel. In this model, P-STS cells react to acetylcholine or histamine with an increase in intracellular calcium mediated by T-type voltage-gated calcium channels followed by serotonin secretion. Incubation with the secondary bile acid deoxycholate inhibited the calcium response to acetylcholine but not to histamine. No response to other nutrients or bacterial products tested (i.e. palmitate, lactate, acetate, proprionate, butyrate, the OR51E1 ligand isovalerate and the HCA2 ligand β-hydroxybutyrate) could be observed. The bile acid receptor TGR5 agonist CCDC did not inhibit the acetylcholine-induced calcium response, and the free fatty acid receptor 2 agonist 4-CMTB had no enhancing effect on the calcium response to acetylcholine. Only butyrate had an enhancing effect on the calcium response in P-STS cells when added for short-time pre-incubation before challenge with acetylcholine. From our data we propose i) an inhibitory effect of deoxycholate at the muscarinic acetylcholine receptor M3 without involvement of TGR5, and that ii) high butyrate concentrations derived from bacterial metabolism of carbohydrates might increase intestinal release of serotonin and potentially also other gut hormones and satiety-inducing peptides independently of known butyrate receptors, thereby influencing intestinal motility and ion secretion.

Background

Type 2 Diabetes Mellitus (T2DM) stands as the foremost risk factor for infected foot ulcers, contributing to a myriad of chronic complications including cardiovascular, renal, neuropathic, vascular, and podiatric issues. Employing suitable antibiotic therapy becomes imperative in managing Diabetic Foot Infections (DFIs). This study endeavors to assess the efficacy of antibiotic treatment in addressing infected foot ulcers among patients with T2DM in Vietnam.

Methods

A descriptive cross-sectional study with analysis was performed on 830 T2DM patients (67 patients with DFIs were treated with antibiotic therapy to evaluate treatment outcomes).

Results

Among T2DM patients, 8.07 % had infected foot ulcers, with an average age of 62.5 ± 11 years and a female-to-male ratio of 2.9:1. Ulcer healing post-antibiotic treatment was 88.06 %, with 35.82 % aligning initial antibiotic treatment with antibiogram results. Bacterial resistance rates were high for Cephalosporin (>60 %), Ampicillin/Sulbactam (91.67 %), and Quinolone groups (>60 %), while Carbapenem group showed high sensitivity (>73 %). Initial empiric antibiotic treatment response was associated with osteomyelitis existence and ulcer healing outcomes (p < 0.005). Wagner grade > 2, elevated CRP levels, and atherosclerotic stenosis were associated with lengthy clinic stays.

Conclusion

Selecting the proper antibiotic regimen is crucial in effectively managing Type 2 Diabetic Foot Infections. Identifying the risk factors associated with treatment outcomes is imperative to mitigate adverse effects on foot infection treatment outcomes among T2DM patients in Vietnam.

Introduction

Metabolic syndrome (MetS) is increasing healthcare costs worldwide. It has been suggested that serum lipin-1 (LPN1) may be associated with components of MetS. The aim of this study was to evaluate LPN1serum levels and its association with MetS components in subjects with and without MetS in this area.

Materials and methods

We included subjects with MetS using the National Cholesterol Education Program, Adult Treatment Panel III criteria. LPN1 levels were measured using the Eliza method.

Results

The results showed that waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG) and triglyceride levels were significantly higher and high density lipoprotein cholesterol and LPN1 levels were significantly lower in subjects with MetS compared to subjects without MetS. There was a significant inverse correlation between LPN1 and FBG, SBP, and DBP in MetS patients. In subjects without MetS, there was no correlation between LPN1and MetS components.

Conclusion

There appears to be a significant association between some components of MetS and serum LPN1 levels. Further studies are needed to elucidate the underlying mechanisms and possible therapeutic implications of this association for the prevention and treatment of MetS-related disorders.