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Medicine Jun 2024The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of non-nitrogen-containing bisphosphonates (non-N-BPs) and nitrogen-containing bisphosphonates (N-BPs) in the treatment of atherosclerosis (AS) and vascular calcification (VC) is uncertain. This meta-analysis was conducted to evaluate the efficacy of non-N-BPs and N-BPs in the treatment of AS and VC.
METHODS
The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched from their inception to July 5th, 2023. Eligible studies comparing bisphosphonates (BPs) versus no BPs in the treatment of AS and VC were included. The data were analyzed using Review Manager Version 5.3.
RESULTS
Seventeen studies were included in this meta-analysis. Twelve were randomized control trials (RCTs), and 5 were nonrandomized studies. Overall, 813 patients were included in the BPs group, and 821 patients were included in the no BPs group. Compared with no BP treatment, non-N-BP or N-BP treatment did not affect serum calcium (P > .05), phosphorus (P > .05) or parathyroid hormone (PTH) levels (P > .05). Regarding the effect on serum lipids, non-N-BPs decreased the serum total cholesterol (TC) level (P < .05) and increased the serum triglyceride (TG) level (P < .01) but did not affect the serum low-density lipoprotein cholesterol (LDL-C) level (P > .05). N-BPs did not affect serum TC (P > .05), TG (P > .05) or LDL-C levels (P > .05). Regarding the effect on AS, non-N-BPs did not have a beneficial effect (P > .05). N-BPs had a beneficial effect on AS, including reducing the intima-media thickness (IMT) (P < .05) and plaque area (P < .01). For the effect on VC, non-N-BPs had a beneficial effect (P < .01), but N-BPs did not have a beneficial effect (P > .05).
CONCLUSION
Non-N-BPs and N-BPs did not affect serum calcium, phosphorus or PTH levels. Non-N-BPs decreased serum TC levels and increased serum TG levels. N-BPs did not affect serum lipid levels. Non-N-BPs had a beneficial effect on VC, and N-BPs had a beneficial effect on AS.
Topics: Humans; Diphosphonates; Atherosclerosis; Vascular Calcification; Nitrogen; Randomized Controlled Trials as Topic; Bone Density Conservation Agents
PubMed: 38847712
DOI: 10.1097/MD.0000000000038404 -
Quantitative Imaging in Medicine and... Jun 2024The application of radiofrequency ablation (RFA) is becoming increasingly widespread in the treatment of primary hyperparathyroidism (PHPT). However, the effect of RFA...
BACKGROUND
The application of radiofrequency ablation (RFA) is becoming increasingly widespread in the treatment of primary hyperparathyroidism (PHPT). However, the effect of RFA treatment on the skeleton in mild PHPT remains unclear. Therefore, the aim of this study was to investigate the change in bone turnover markers and bone mineral density (BMD) before and 2 years after RFA in patients with mild PHPT.
METHODS
In this open-label, prospective study, 81 patients with mild PHPT including 36 treated with RFA and 45 observed without intervention (OBS), along with 81 age-matched healthy controls, were enrolled from November 2018 to September 2021 at Gansu Provincial Hospital. The main outcome measures were levels of serum calcium, serum intact parathyroid hormone (iPTH), and bone turnover markers, including bone-specific alkaline phosphatase (ALP), C-terminal cross-linking telopeptides of type I collagen (β-CTx), and osteocalcin (OC). BMD (femoral neck and lumbar spine) was measured with dual-energy X-ray absorptiometry, and spine radiographs were obtained for vertebral fracture assessment. Paired and unpaired two-tailed -tests and Spearman rank correlation coefficient were used for statistical analyses.
RESULTS
Normalized outcomes for both iPTH and calcium levels were achieved in 32 of 36 (88.9%) patients with mild PHPT treated with RFA. There was a significant treatment effect of RFA on bone turnover biomarkers compared with OBS before the treatment (P=0.04) and at the end of follow-up or (P=0.03). BMD of the lumbar spine increased by 1.8% (P=0.03) and remained stable in the femoral neck (P=0.17) after RFA. However, there was an obvious treatment effect of RFA on BMD compared with OBS (P 0.04). The only compartment with a T-score increase in the RFA group was the lumbar spine in (P<0.001). There was no difference in fracture frequency between groups during the follow-up period.
CONCLUSIONS
RFA can improve serum bone turnover markers in patients with mild PHPT and can be expected to increase BMD in the L1-L4 vertebrae and preserve BMD in the femoral neck. Whether RFA can reduce fracture risk in the long-term is a clinical concern for patients with mild PHPT.
PubMed: 38846300
DOI: 10.21037/qims-23-1719 -
Scientific Reports Jun 2024The TBS is a new method for clinicians to assess the bone quality. It is directly related to the mechanical strength of bone and helps predict fracture risk. The present...
The TBS is a new method for clinicians to assess the bone quality. It is directly related to the mechanical strength of bone and helps predict fracture risk. The present analysis aimed to investigate the associations between serum PTH levels and TBS by analyzing data from the National Health and Nutrition Examination Survey (NHANES). A total of 3516 participants from the NHANES 2005-2006 were included in this cross-sectional study. The independent variable was serum PTH, and the outcome variable was TBS. The associations of serum PTH levels with TBS were examined using multivariable linear regression models. After adjusting for covariates, there was a negative association between serum PTH level and TBS (β = - 0.0034; 95% confidence interval, - 0.0050 to - 0.0017). However, in the subgroup analysis stratified by gender, race, and age, this association became negative only in Non-Hispanic White (β = - 0.0047, 95% CI: - 0.0071 to - 0.0048) and young people (age < 60) (β = - 0.0036, 95% CI: - 0.0057, - 0.0016), regardless of gender. In addition, the association of serum PTH with TBS was an U-shaped curve, with a point of inflection at 6.71 pmol/L. This study showed that serum PTH level was negatively associated with TBS. Maintaining PTH levels in a lower reasonable clinical range may be beneficial to bone health, especially for young non-Hispanic white.
Topics: Humans; Parathyroid Hormone; Male; Female; Cross-Sectional Studies; Middle Aged; Cancellous Bone; Adult; Nutrition Surveys; Bone Density; Aged
PubMed: 38844829
DOI: 10.1038/s41598-024-63979-9 -
Obesity Surgery Jun 2024The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not...
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.
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