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Obesity Surgery Jul 2024The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not... (Observational Study)
Observational Study
PURPOSE
The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not yet fully understood in pregnant women after BS.
MATERIAL AND METHODS
This single-center retrospective observational cohort study includes all women with a first and single pregnancy after BS who completed at least one clinical and biological nutritional assessment during pregnancy between 2010 and 2016. The quarterly biological assessment comprised blood count, ferritin, calcium, 25OH vitamin D, parathyroid hormone, fasting glucose, albumin, prealbumin, vitamin A, vitamin B12, folic acid, and zinc.
RESULTS
Among 120 pregnancies analysed, two-thirds underwent gastric bypass (Roux-en-Y and one-anastomosis) and one-third a restrictive procedure (adjustable gastric band or sleeve gastrectomy). The median [Q1-Q3] preoperative BMI was 43.8 [41.1-47.7] kg/m and the mean age at pregnancy was 32.6 ± 5.3 years. Weight loss and time from surgery to pregnancy were 35.1 ± 15.4 kg and 2.9 [1.3-4.5] years, respectively. Ten women (8%) gave birth prematurely, and 22 newborns (19%) were SGA. Univariate analysis shows that ferritin was significantly higher in mothers with SGA than in those without SGA (35.5 [22.3-69.5] vs. 15 [10-32] ng/ml) at third trimester of pregnancy. Women who received pre-pregnancy nutritional assessment seemed less likely to give birth to a SGA newborn (32% vs. 54%, p = 0.07).
CONCLUSION
Iron supplementation should be carefully prescribed and closely monitored during pregnancy in women who have undergone BS.
Topics: Humans; Female; Pregnancy; Adult; Retrospective Studies; Ferritins; Pregnancy Outcome; Infant, Newborn; Infant, Small for Gestational Age; Bariatric Surgery; Obesity, Morbid; Birth Weight; Pregnancy Complications
PubMed: 38842761
DOI: 10.1007/s11695-024-07285-3 -
Restorative Dentistry & Endodontics May 2024This study evaluated the effect of serum calcium, parathyroid hormone (PTH), vitamin D, and uric acid levels on pulp stone formation.
OBJECTIVES
This study evaluated the effect of serum calcium, parathyroid hormone (PTH), vitamin D, and uric acid levels on pulp stone formation.
MATERIALS AND METHODS
Patients who were admitted to the Muğla Sıtkı Koçman University, Faculty of Dentistry, Department of Oral and Maxillofacial Radiology for dental complaints were registered. Among these patients, individuals who had routine biochemical tests at the same period in the Outpatient Clinics of Muğla Sıtkı Koçman University Training and Research Hospital were included in the study. The patients with at least 1 pulp stone on panoramic radiographs recorded as the "pulp stone group" while patients without any pulp stones were the "control group". Demographic data and serum levels of calcium, PTH, vitamin D, and uric acid were retrospectively evaluated in both groups. Student -test or Mann-Whitney test was used to evaluate the differences between the groups.
RESULTS
Among 151 patients, dental pulp stone was detected in 53.6% of patients, and 82.7% of these patients were female. Female sex and pulp stone formation were significantly associated ( = 0.001). The mean age of the pulp stone group was 43.9, while it was 39.9 in the control group, without any significant correlation between age and pulp stone ( > 0.05). Similarly, there were no significant differences in serum levels of PTH, vitamin D, uric acid and calcium between groups ( > 0.05).
CONCLUSIONS
According to the present study, the effect of dental factors rather than systemic factors should be considered primarily in pulp stone formation.
PubMed: 38841388
DOI: 10.5395/rde.2024.49.e17 -
Frontiers in Endocrinology 2024Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of...
Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of parathyroid lesions. We report here the case of a 30 year-old woman with a fortuitously discovered 2 cm cervical mass for which a parathyroid origin was originally suspected due to its retro-thyroidal localization and a personal history of nephrolithiasis. Normal serum calcium and parathyroid hormone (PTH) levels excluded primary hyperparathyroidism, raising suspicion of a non-functional parathyroid adenoma, and SPECT/CT imaging showed that the mass was Tc-sestamibi-avid. Fine-needle aspiration (FNA) was performed; cytology was non-diagnostic but the needle washout was negative for thyroglobulin, calcitonin and PTH, arguing against a thyroidal or parathyroidal origin of the mass. Core needle biopsy revealed a schwannoma, ostensibly originating from the recurrent laryngeal nerve; upon surgical resection, it was finally found to arise from the esophageal submucosa. This case illustrates the fact that endocrinologists, radiologists, nuclear medicine, head and neck, and other specialists investigating patients with cervical masses should be aware that schwannomas need to be considered in the differential diagnosis of focal Tc-sestamibi uptake in the neck region.
Topics: Humans; Female; Technetium Tc 99m Sestamibi; Parathyroid Neoplasms; Adult; Neurilemmoma; Diagnosis, Differential; Adenoma; Esophageal Neoplasms; Single Photon Emission Computed Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 38841301
DOI: 10.3389/fendo.2024.1258233 -
BMC Musculoskeletal Disorders Jun 2024Osteoporosis (OS) is a systemic bone disease characterized by low bone mass and bone microstructure damage. This study.
OBJECTIVE
Osteoporosis (OS) is a systemic bone disease characterized by low bone mass and bone microstructure damage. This study.
METHODS
According to the T value, 88 elderly fracture patients were grouped as the control group (without OS, 43 cases) and observation group (with T value <-2.5, which could be diagnosed as OS, 45 cases). The content of boney containing protein (BGP), total type 1 collagen amino terminal extender peptide (TPINP), β-Crosslaps (β-CTX), parathyroid hormone (PTH) and insulin-like growth factors-1 (IGF-1) was compared. Multivariate logistic regression was adopted to analyze the correlation between biochemical indexes and the occurrence of senile OS fracture and the related risk factors. The diagnostic value in the elderly was analyzed by receiver operating characteristic (ROC) curve.
RESULTS
The levels of BGP, TPINP, β-CTX, PTH and IGF-1 were elevated, and the level of IGF-1 was decreased in the observation group compared with the control group (P < 0.05). The elevated content of BGP, TPINP, β-CTX and PTH, and the decreased expression of IGF-1 were influencing factors for OS fractures in the elderly (P < 0.05). The sensitivity and specificity to predict the occurrence of OS fractures in the elderly were 91.70% and 90.50%, respectively. The AUC of combined detection was 0.976 (95% CI: 0.952-1.000), which was memorably higher than single indicator detection (P < 0.05). Among 45 patients, 32 cases had good prognosis and 13 had poor prognosis. In comparison with the good prognosis group, the content of BGP, TPINP, β-CTX and PTH were sensibly higher, the level of IGF-1 was prominently lower, and the proportion of fracture history was much higher in poor prognosis group (P < 0.05). Fracture history, BGP, TPINP, β-CTX, PTH and IGF-1 were independent risk factors for poor prognosis of elderly OS fractures (P < 0.05).
CONCLUSION
Bone metabolism factors were associated with poor prognosis of OS in the elderly. The combined detection had higher diagnostic value in calculating the risk of OS fracture in the elderly than single indicator detection.
Topics: Humans; Aged; Female; Male; Osteoporotic Fractures; Risk Factors; Insulin-Like Growth Factor I; Aged, 80 and over; Parathyroid Hormone; Biomarkers; Osteoporosis; Predictive Value of Tests; Collagen Type I; ROC Curve; Case-Control Studies; Risk Assessment; Middle Aged
PubMed: 38840246
DOI: 10.1186/s12891-024-07560-5 -
Microbial Cell Factories Jun 2024Recombinant peptide production in Escherichia coli provides a sustainable alternative to environmentally harmful and size-limited chemical synthesis. However, in-vivo...
BACKGROUND
Recombinant peptide production in Escherichia coli provides a sustainable alternative to environmentally harmful and size-limited chemical synthesis. However, in-vivo production of disulfide-bonded peptides at high yields remains challenging, due to degradation by host proteases/peptidases and the necessity of translocation into the periplasmic space for disulfide bond formation.
RESULTS
In this study, we established an expression system for efficient and soluble production of disulfide-bonded peptides in the periplasm of E. coli. We chose model peptides with varying complexity (size, structure, number of disulfide bonds), namely parathyroid hormone 1-84, somatostatin 1-28, plectasin, and bovine pancreatic trypsin inhibitor (aprotinin). All peptides were expressed without and with the N-terminal, low molecular weight CASPON™ tag (4.1 kDa), with the expression cassette being integrated into the host genome. During BioLector™ cultivations at microliter scale, we found that most of our model peptides can only be sufficiently expressed in combination with the CASPON™ tag, otherwise expression was only weak or undetectable on SDS-PAGE. Undesired degradation by host proteases/peptidases was evident even with the CASPON™ tag. Therefore, we investigated whether degradation happened before or after translocation by expressing the peptides in combination with either a co- or post-translational signal sequence. Our results suggest that degradation predominantly happened after the translocation, as degradation fragments appeared to be identical independent of the signal sequence, and expression was not enhanced with the co-translational signal sequence. Lastly, we expressed all CASPON™-tagged peptides in two industry-relevant host strains during C-limited fed-batch cultivations in bioreactors. We found that the process performance was highly dependent on the peptide-host-combination. The titers that were reached varied between 0.6-2.6 g L, and exceeded previously published data in E. coli. Moreover, all peptides were shown by mass spectrometry to be expressed to completion, including full formation of disulfide bonds.
CONCLUSION
In this work, we demonstrated the potential of the CASPON™ technology as a highly efficient platform for the production of soluble peptides in the periplasm of E. coli. The titers we show here are unprecedented whenever parathyroid hormone, somatostatin, plectasin or bovine pancreatic trypsin inhibitor were produced in E. coli, thus making our proposed upstream platform favorable over previously published approaches and chemical synthesis.
Topics: Escherichia coli; Periplasm; Disulfides; Peptides; Recombinant Proteins; Aprotinin
PubMed: 38840157
DOI: 10.1186/s12934-024-02446-6 -
European Journal of Nuclear Medicine... Jun 2024We conducted a cost-effectiveness analysis in which we compared a preoperative [F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in...
PURPOSE
We conducted a cost-effectiveness analysis in which we compared a preoperative [F]Fluorocholine PET/CT-based one-stop-shop imaging strategy with current best practice in which [F]Fluorocholine PET/CT is only recommended after negative or inconclusive [Tc]Tc-methoxy isobutyl isonitrile SPECT/CT for patients suffering from primary hyperparathyroidism. We investigated whether the one-stop-shop strategy performs as well as current best practice but at lower costs.
METHODS
We developed a cohort-level state transition model to evaluate both imaging strategies respecting an intraoperative parathyroid hormone monitored treatment setting as well as a traditional treatment setting. The model reflects patients' hospital journeys after biochemically diagnosed primary hyperparathyroidism. A cycle length of twelve months and a lifetime horizon were used. We conducted probabilistic analyses simulating 50,000 cohorts to assess joint parameter uncertainty. The incremental net monetary benefit and cost for each quality-adjusted life year were estimated. Furthermore, threshold analyses regarding the tariff of [F]Fluorocholine PET/CT and the sensitivity of [Tc]Tc-methoxy isobutyl isonitrile SPECT/CT were performed.
RESULTS
The simulated long-term health effects and costs were similar for both imaging strategies. Accordingly, there was no incremental net monetary benefit and the one-stop-shop strategy did not result in lower costs. These results applied to both treatment settings. The threshold analysis indicated that a tariff of €885 for [F]Fluorocholine PET/CT was required to be cost-effective compared to current best practice.
CONCLUSION
Both preoperative imaging strategies can be used interchangeably. Daily clinical practice grounds such as available local resources and patient preferences should inform policy-making on whether a hospital should implement the one-stop-shop imaging strategy.
PubMed: 38837058
DOI: 10.1007/s00259-024-06771-1 -
Journal of Nephrology Jun 2024X-linked hypophosphatemia (XLH) represents the most prevalent cause of hereditary hypophosphatemia. X-linked hypophosphatemia causes an elevation of fibroblast growth...
BACKGROUND
X-linked hypophosphatemia (XLH) represents the most prevalent cause of hereditary hypophosphatemia. X-linked hypophosphatemia causes an elevation of fibroblast growth factor 23 (FGF23), a hormone responsible for inducing hyperphosphaturia, and reduced active vitamin D synthesis. Challenges in diagnosis and the absence of well-defined clinical guidelines have resulted in higher rates of late diagnoses. While numerous reports focus on pediatric X-linked hypophosphatemia patients, studies in adults are limited.
METHODS
Multicenter, cross-sectional, observational study of a cohort of adult patients diagnosed with X-linked hypophosphatemia. The study identified demographic, clinical, genetic, laboratory variables, treatments used, comorbidities, and complications.
RESULTS
Twenty patients diagnosed with X-linked hypophosphatemia were collected. The median age at diagnosis was 11 (1-56) years and at data collection was 44 (21-68) years. Fifty percent of cases were diagnosed in adulthood. Main clinical manifestation was osteoarticular pain, in 75% of cases, and no relation to age at diagnosis, height, phosphorus, or parathyroid hormone (PTH) levels was observed (p > 0.05). Lower limb deformities were associated with reduced stature and earlier diagnosis (p < 0.05). Sixty percent of patients reported pain requiring chronic medication and no significant correlation was found with other variables. Anxiety and depression were found in an important number of patients. FGF23 levels were not related to any of the clinical variables studied (p > 0.05).
DISCUSSION
This is the largest study on adult patients with X-linked hypophosphatemia in southern Europe. It may offer valuable insights into the natural progression and course of the condition in adults, which can aid in better clinical management.
PubMed: 38837007
DOI: 10.1007/s40620-024-01962-3 -
Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration.Lab on a Chip Jun 2024The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH)....
The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.
Topics: Parathyroid Hormone; Calcium; Humans; Lab-On-A-Chip Devices; Parathyroid Glands; Mesenchymal Stem Cells; Organoids; Cells, Cultured
PubMed: 38836406
DOI: 10.1039/d4lc00249k -
Kidney Diseases (Basel, Switzerland) Jun 2024This study aimed to develop and validate machine learning (ML) models based on serum Klotho for predicting end-stage kidney disease (ESKD) and cardiovascular disease...
INTRODUCTION
This study aimed to develop and validate machine learning (ML) models based on serum Klotho for predicting end-stage kidney disease (ESKD) and cardiovascular disease (CVD) in patients with chronic kidney disease (CKD).
METHODS
Five different ML models were trained to predict the risk of ESKD and CVD at three different time points (3, 5, and 8 years) using a cohort of 400 non-dialysis CKD patients. The dataset was divided into a training set (70%) and an internal validation set (30%). These models were informed by data comprising 47 clinical features, including serum Klotho. The best-performing model was selected and used to identify risk factors for each outcome. Model performance was assessed using various metrics.
RESULTS
The findings showed that the least absolute shrinkage and selection operator regression model had the highest accuracy (C-index = 0.71) in predicting ESKD. The features mainly included in this model were estimated glomerular filtration rate, 24-h urinary microalbumin, serum albumin, phosphate, parathyroid hormone, and serum Klotho, which achieved the highest area under the curve (AUC) of 0.930 (95% CI: 0.897-0.962). In addition, for the CVD risk prediction, the random survival forest model with the highest accuracy (C-index = 0.66) was selected and achieved the highest AUC of 0.782 (95% CI: 0.633-0.930). The features mainly included in this model were age, history of primary hypertension, calcium, tumor necrosis factor-alpha, and serum Klotho.
CONCLUSION
We successfully developed and validated Klotho-based ML risk prediction models for CVD and ESKD in CKD patients with good performance, indicating their high clinical utility.
PubMed: 38835404
DOI: 10.1159/000538510 -
BMC Musculoskeletal Disorders Jun 2024Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is...
BACKGROUND
Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is still largely unknown. In this study, we aim to evaluate the predictive power of different ML algorithms in this area and identify key features associated with the risk of subsequent fragility fractures in osteoporotic patients.
METHODS
We retrospectively analyzed data from patients presented with fragility fractures at our Fracture Liaison Service, categorizing them into index fragility fracture (n = 905) and subsequent fragility fracture groups (n = 195). We independently trained ML models using 27 features for both male and female cohorts. The algorithms tested include Random Forest, XGBoost, CatBoost, Logistic Regression, LightGBM, AdaBoost, Multi-Layer Perceptron, and Support Vector Machine. Model performance was evaluated through 10-fold cross-validation.
RESULTS
The CatBoost model outperformed other models, achieving 87% accuracy and an AUC of 0.951 for females, and 93.4% accuracy with an AUC of 0.990 for males. The most significant predictors for females included age, serum C-reactive protein (CRP), 25(OH)D, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), femoral neck Z-score, menopause age, number of pregnancies, phosphorus, calcium, and body mass index (BMI); for males, the predictors were serum CRP, femoral neck T-score, PTH, hip T-score, BMI, BUN, creatinine, alkaline phosphatase, and spinal Z-score.
CONCLUSION
ML models, especially CatBoost, offer a valuable approach for predicting subsequent fragility fractures in osteoporotic patients. These models hold the potential to enhance clinical decision-making by supporting the development of personalized preventative strategies.
Topics: Humans; Male; Female; Machine Learning; Aged; Retrospective Studies; Osteoporotic Fractures; Middle Aged; Aged, 80 and over; Predictive Value of Tests; Risk Assessment; Risk Factors; Osteoporosis; Algorithms
PubMed: 38834975
DOI: 10.1186/s12891-024-07559-y