Do men improve their bone mineral density 1 year after parathyroidectomy for primary hyperparathyroidism? Results of a prospective study.

BACKGROUND: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. METHODS: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. RESULTS: Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). CONCLUSION: Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

CONTEXT: Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. OBJECTIVE: To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. DESIGN: In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. SETTING: Referral center. PATIENTS: A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURE: BMD change between before and 1 year after parathyroidectomy. RESULTS: Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. CONCLUSION: Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

Insulin Growth Factor-1 Status in Hidradenitis Suppurativa: A French Institutional Pilot Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the follicles in the apocrine glands and is associated with a deficiency in the innate immunity of the skin. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. OBJECTIVE: Although a relationship has already been demonstrated between HS and innate immunity, IGF-1 status in patients with HS is still unknown. The objective of this pilot study was to determine IGF-1 status in patients with HS as well as its potential relationship with the clinical profile of the disease. METHODS: This monocentric and cross-sectional study involved 39 patients hospitalized at the Dermatology Department of CHU Nantes between November 2014 and January 2018. Clinical data and IGF1 status were collected during the follow-up consultation. RESULTS: Forty-nine percent of the patients had very low levels of IGF-1. At the clinical level, these patients were young and with a short duration of disease. The major difference was that IGF1-deficient patients had a higher BMI than others. The others factors differing between the two patient groups did not reach statistical significance. CONCLUSION: This exploratory pilot study indicates that HS with a low level of IGF-1 could represent a specific phenotype of patients with HS. These preliminary results have to be confirmed with a larger cohort, as they could have practical consequences in the therapeutic care of these patients.

Insulin: Know what your immunoassay detects. Evaluation of two new immunoassays.

BACKGROUND: Insulin is essential for glycemic regulation but diseases can cause a default or an excess of insulin secretion leading to dysregulated glycemia. Hence, measurement of insulinemia is useful to investigate hypoglycemia, determine the pathogenesis of diabetes and evaluate ß-cell function. Thus, diabetic patients need supplementation with recombinant human insulin and/or insulin analogues. Analogues have primary sequences different from native human insulin and may not be detected by some immunoassays. The objective of our study was to evaluate new insulin immunoassays by determining their ability to detect different types of human insulin or analogues. METHODS: This study compared the reactivity of two new insulin immunoassays with five well-established immunoassays on ten commercial insulins. We also measured insulin in blood samples from diabetic or pancreas transplant patients with known treatment. RESULTS: Contrary to recombinant human insulin, there were differences in the specificity to insulin analogues. We distinguished three immunoassay categories: those recognizing all types of insulin such as the non-specific BI-INS-IRMA®, Architect® and Access® immunoassays; those recognizing human insulin only (Cobas®); and those recognizing human insulin and analogues in variable proportions (Liaison XL®, iFlash® and Maglumi®). CONCLUSION: An accurate biological interpretation of insulinemia relies on knowledge of the specificity of the immunoassay used.

Crosstalk between omega-6 oxylipins and the enteric nervous system: Implications for gut disorders?

The enteric nervous system (ENS) continues to dazzle scientists with its ability to integrate signals, from the outside as well as from the host, to accurately regulate digestive functions. Composed of neurons and enteric glial cells, the ENS interplays with numerous neighboring cells through the reception and/or the production of several types of mediators. In particular, ENS can produce and release n-6 oxylipins. These lipid mediators, derived from arachidonic acid, play a major role in inflammatory and allergic processes, but can also regulate immune and nervous system functions. As such, the study of these n-6 oxylipins on the digestive functions, their cross talk with the ENS and their implication in pathophysiological processes is in full expansion and will be discussed in this review.

Psychological stress induces an increase in cholinergic enteric neuromuscular pathways mediated by glucocorticoid receptors.

Introduction: Repeated acute stress (RASt) is known to be associated with gastrointestinal dysfunctions. However, the mechanisms underlying these effects have not yet been fully understood. While glucocorticoids are clearly identified as stress hormones, their involvement in RASt-induced gut dysfunctions remains unclear, as does the function of glucocorticoid receptors (GR). The aim of our study was to evaluate the involvement of GR on RASt-induced changes in gut motility, particularly through the enteric nervous system (ENS). Methods: Using a murine water avoidance stress (WAS) model, we characterized the impact of RASt upon the ENS phenotype and colonic motility. We then evaluated the expression of glucocorticoid receptors in the ENS and their functional impact upon RASt-induced changes in ENS phenotype and motor response. Results: We showed that GR were expressed in myenteric neurons in the distal colon under basal conditions, and that RASt enhanced their nuclear translocation. RASt increased the proportion of ChAT-immunoreactive neurons, the tissue concentration of acetylcholine and enhanced cholinergic neuromuscular transmission as compared to controls. Finally, we showed that a GR-specific antagonist (CORT108297) prevented the increase of acetylcholine colonic tissue level and in vivo colonic motility. Discussion: Our study suggests that RASt-induced functional changes in motility are, at least partly, due to a GR-dependent enhanced cholinergic component in the ENS.

A novel fully-automated method to measure steroids in serum by liquid chromatography-tandem mass spectrometry.

Background: Steroids play a key role in numerous physiological processes. Steroid determination is a useful tool to explore various endocrine diseases. Because of its specificity, mass spectrometry is considered to be a reference method for the determination of steroids in serum compared to radioimmunoassay. This technology could progress towards more automation for the optimal organization of clinical laboratories and ultimately for the benefit of patients. Methods: A fully automated ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed and fully validated to determine five steroids in serum. Sample preparation was based on protein precipitation with filtration followed by online solid phase extraction. Chromatographic separation was performed using a biphenyl stationary phase. Results: The method was successfully validated according to European Medicine Agency guidelines. Coefficients of variation did not exceed, respectively, 8.4% and 8.1% for intra- and inter-assay precision. Method comparison with radioimmunoassay showed a proportional bias for all compounds, except for testosterone in men. Comparison with another LC-MS/MS method demonstrated acceptable concordance for all steroids, although a small bias was observed for androstenedione. Conclusion: The novelty of this method is that it has been fully automated. Automation provides benefits in traceability and allows significant savings in cost and time.

Impact of empowering leadership on emotional exhaustion: A controlled interventional study in a large French university hospital complex.

AIM: The aim of this study is to assess the effect of a systemic intervention on the evolution of empowering leadership and emotional exhaustion in a university hospital sub-centre compared to a control sub-centre, both being part of a large French university hospital complex. BACKGROUND: Empowering leadership is a promising strategy for developing hospital team engagement and performance. However, the bureaucratic functioning of large hospitals, characterized by a managerial culture of control and a stratified organization, can be a barrier to empowering leadership. METHODS: The intervention included empowering leadership training, direct field experimentation of empowering leadership and coaching, involving all the sub-centre hierarchical levels for 12 months. Data were collected before and after the intervention. A total of 441 and 310 participants were, respectively, included in the intervention and control sub-centres. RESULTS: Empowering leadership was decreased, and emotional exhaustion was increased in the control sub-centre, while the scores remained stable in the intervention sub-centre. The increased emotional exhaustion in the control sub-centre could partially be explained by the change in empowering leadership. CONCLUSION: In a context of decreased empowering leadership and increased emotional exhaustion, the intervention had a protective effect. Implications for the design of future interventions were discussed. IMPLICATIONS FOR NURSING MANAGEMENT: This study unequivocally showed the benefit of transforming hospital management towards empowering leadership, to prevent increased emotional exhaustion. REGISTRATION NUMBER: This study is registered on ClinicalTrials.gov on 4 July 2019 (NCT04010773).

Feasibility of Combining Transcranial Direct Current Stimulation and Active Fully Embodied Virtual Reality for Visual Height Intolerance: A Double-Blind Randomized Controlled Study.

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) and Virtual Reality Exposure Therapy (VRET) are individually increasingly used in psychiatric research. OBJECTIVE/HYPOTHESIS: Our study aimed to investigate the feasibility of combining tDCS and wireless 360° full immersive active and embodied VRET to reduce height-induced anxiety. METHODS: We carried out a pilot randomized, double-blind, controlled study associating VRET (two 20 min sessions with a 48 h interval, during which, participants had to cross a plank at rising heights in a building in construction) with online tDCS (targeting the ventromedial prefrontal cortex) in 28 participants. The primary outcomes were the sense of presence level and the tolerability. The secondary outcomes were the anxiety level (Subjective Unit of Discomfort) and the salivary cortisol concentration. RESULTS: We confirmed the feasibility of the association between tDCS and fully embodied VRET associated with a good sense of presence without noticeable adverse effects. In both groups, a significant reduction in the fear of height was observed after two sessions, with only a small effect size of add-on tDCS (0.1) according to the SUD. The variations of cortisol concentration differed in the tDCS and sham groups. CONCLUSION: Our study confirmed the feasibility of the association between wireless online tDCS and active, fully embodied VRET. The optimal tDCS paradigm remains to be determined in this context to increase effect size and then adequately power future clinical studies assessing synergies between both techniques.

123I Scintigraphy Mirror Image of Graves Disease Induced by Radioiodine Treatment for Toxic Adenoma.

ABSTRACT: A 61-year-old woman presenting with hyperthyroidism received 131I therapy for a toxic adenoma diagnosed by 123I scintigraphy. Six months later, the patient had a relapse of hyperthyroidism, and 123I scintigraphy showed a mirror image of the first scintigraphy: a high and diffuse uptake in the thyroid gland except for the previously treated nodule. Graves disease was confirmed by elevated thyrotropin receptor antibodies. The patient was cured by a second radioiodine therapy. Radioiodine-induced Graves disease may occur within 6 months of 131I treatment of toxic adenoma and can be treated with a second line of 131I.

Analytical validation of eight methods of thyroglobulin measurement in fine-needle aspiration washouts.

BACKGROUND: Thyroglobulin (Tg) assay in washout fluids of fine needles, after cervical lymph nodes aspiration, is used for detecting metastases from differentiated thyroid carcinomas. Assay methods are the same as for Tg in serum. However, with non-serum samples, methods require extensive validation to notably check for the absence of matrix effect. This study fits this context. Our objectives were to assess analytic performances, in washout fluid, of eight different Tg assay methods and to compare them to validated data in serum. METHODS: Eleven medical laboratories participated in this study. The matrix tested was phosphate-buffer saline containing 1% bovine serum albumin (PBS-1% BSA). Samples used were dilutions, in this buffer, of Certified Reference Material (CRM 457). We verified, for all methods, the limit of detection, precision, linearity, trueness and accuracy. RESULTS: In PBS-1% BSA, the functional sensitivities (FS) were comparable to those expected for serum. All the methods were linear. The relative biases of trueness were between -24.5 and 10.2% around 1 µg/L. Total analytical error was ≤40% near the functional sensitivity values. CONCLUSION: No quantitatively important matrix effect was observed. All the methods showed their ability to measure Tg in PBS-1% BSA, over the concentration range of interest, with acceptable total analytical error. We validated the functional sensitivity value as a decision threshold in thyroidectomized patients after treatment and with low concentrations of serum Tg.

A high-throughput mass spectrometry-based assay for large-scale profiling of circulating human apolipoproteins.

Apolipoproteins govern lipoprotein metabolism and are promising biomarkers of metabolic and cardiovascular diseases. Unlike immunoassays, MS enables the quantification and phenotyping of multiple apolipoproteins. Hence, here, we aimed to develop a LC-MS/MS assay that can simultaneously quantitate 18 human apolipoproteins [A-I, A-II, A-IV, A-V, B48, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a)] and determined apoE, apoL1, and apo(a) phenotypes in human plasma and serum samples. The plasma and serum apolipoproteins were trypsin digested through an optimized procedure and peptides were extracted and analyzed by LC-MS/MS. The method was validated according to standard guidelines in samples spiked with known peptide amounts. The LC-MS/MS results were compared with those obtained with other techniques, and reproducibility, dilution effects, and stabilities were also assessed. Peptide markers were successfully selected for targeted apolipoprotein quantification and phenotyping. After optimization, the assay was validated for linearity, lower limits of quantification, accuracy (biases: -14.8% to 12.1%), intra-assay variability [coefficients of variation (CVs): 1.5-14.2%], and inter-assay repeatability (CVs: 4.1-14.3%). Bland-Altman plots indicated no major statistically significant differences between LC-MS/MS and other techniques. The LC-MS/MS results were reproducible over five repeated experiments (CVs: 1.8-13.7%), and we identified marked differences among the plasma and serum samples. The LC-MS/MS assay developed here is rapid, requires only small sampling volumes, and incurs reasonable costs, thus making it amenable for a wide range of studies of apolipoprotein metabolism. We also highlight how this assay can be implemented in laboratories.

Cortisol total/CRP ratio for the prediction of hospital-acquired pneumonia and initiation of corticosteroid therapy in traumatic brain-injured patients.

BACKGROUND: To propose a combination of blood biomarkers for the prediction of hospital-acquired pneumonia (HAP) and for the selection of traumatic brain-injured (TBI) patients eligible for corticosteroid therapy for the prevention of HAP. METHODS: This was a sub-study of the CORTI-TC trial, a multicenter, randomized, double-blind, controlled trial evaluating the risk of HAP at day 28 in 336 TBI patients treated or not with corticosteroid therapy. Patients were between 15 and 65 years with severe traumatic brain injury (Glasgow coma scale score ≤ 8 and trauma-associated lesion on brain CT scan) and were enrolled within 24 h of trauma. The blood levels of CRP and cortisoltotal&free, as a surrogate marker of the pro/anti-inflammatory response balance, were measured in samples collected before the treatment initiation. Endpoint was HAP on day 28. RESULTS: Of the 179 patients with available samples, 89 (49.7%) developed an HAP. Cortisoltotal&free and CRP blood levels upon ICU admission were not significantly different between patients with or without HAP. The cortisoltotal/CRP ratio upon admission was 2.30 [1.25-3.91] in patients without HAP and 3.36 [1.74-5.09] in patients with HAP (p = 0.021). In multivariate analysis, a cortisoltotal/CRP ratio > 3, selected upon the best Youden index on the ROC curve, was independently associated with HAP (OR 2.50, CI95% [1.34-4.64] p = 0.004). The HR for HAP with corticosteroid treatment was 0.59 (CI95% [0.34-1.00], p = 0.005) in patients with a cortisoltotal/CRP ratio > 3, and 0.89 (CI95% [0.49-1.64], p = 0.85) in patients with a ratio < 3. CONCLUSION: A cortisoltotal/CRP ratio > 3 upon admission may predict the development of HAP in severe TBI. Among these patients, corticosteroids reduce the occurrence HAP. We suggest that this ratio may select the patients who may benefit from corticosteroid therapy for the prevention of HAP.

Impact at two years of an intervention on empowerment among medical care teams: study protocol of a randomised controlled trial in a large French university hospital.

BACKGROUND: Empowerment of hospital workers is known as a key factor of organizational performance and occupational health. Nevertheless, empowering workers remains a real challenge. As in many traditional organizations, hospitals follow a bureaucratic model defined by a managerial culture of control and a stratified organization, which at once weaken professionals' mastery of their work and hinder their commitment and performance. Based on the existing literature this protocol describes a new managerial and organizational transformation program as well as the study design of its effect on worker empowerment in a large French public hospital. The project is funded by the French Ministry of Health for a total of 498,180 €. METHODS: This study is a randomized controlled trial conducted in a French university hospital complex (CHU). The CHU comprises 12 sub-centers (SC) with about 20 care units and 1000 employees each. Randomization is performed at SC level. The intervention lasts 12 months and combines accompaniment of healthcare teams, frontline managers and SC directors to empower first-line professionals in the experimental SC. Quantitative outcome measurements are collected over 2 years during mandatory check-ups in the occupational medicine department. The primary outcomes are structural and psychological empowerment, motivational processes, managerial practices, working conditions, health and performance. Mixed linear modeling is the primary data analysis strategy. DISCUSSION: The protocol was approved by the CHU health ethics committee. The results of the analysis of the intervention effects will be reported in a series of scientific articles. The results will contribute to reflection on prevention and management policies, and to the development of Workplace Quality-of-Life. If the intervention is a success, the system will warrant replication in other SCs and in other health facilities. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov on July 4, 2019 (NCT04010773).

Abnormally Elevated Follicle-Stimulating Hormone (FSH) Level in an Infertile Woman.

We report a case of 33-year-old woman with a 4-year primary infertility. A high isolated follicle-stimulating hormone (FSH) level was conflicting with the clinical situation and with other hormonal markers which were in favor of polycystic ovarian syndrome. We followed a strategy used to identify immune complexes involving FSH. The PEG precipitation test revealed that the high FSH level was almost exclusively due to the presence of autoimmune FSH immunoglobulin complex (macro-FSH). The profile obtained by gel filtration chromatography confirmed the presence of an FSH-immunoglobulin complex. Such immunological dysregulation could be explored in cases of unexplained infertility and recurrent IVF failure.

Prevalence of hypobetalipoproteinemia and related psychiatric characteristics in a psychiatric population: results from the retrospective HYPOPSY Study.

BACKGROUND: Hypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders. METHODS: HYPOPSY is a retrospective study including 839 adults hospitalized in the Psychiatry department of Nantes University Hospital during the year 2014, except patients with eating disorders. The prevalence of primary HBL was defined by a plasma LDL-C concentration ≤ 50 mg/dL. Secondary causes of HBL were excluded after a review of medical records (n=2). Related-psychiatric disorders in patients with and without HBL were recorded using the ICD-10 classification. RESULTS: Twenty cases of primary HBL (mean [SD] LDL-C: 42 [7] mg/dL) were diagnosed, leading to a prevalence of 2.39%. In comparison, the prevalence of HBL in a healthy control population was 0.57%. Psychiatric patients with HBL were characterized by a higher frequency of schizophrenia (p=0.044), hetero-aggression (p=0.015) and pervasive and specific developmental disorders (including autism) (p=0.011). CONCLUSIONS: The prevalence of HBL is 4-fold higher in psychiatric than in general population. More specifically, some statistically significant associations were found between low LDL-C concentrations and schizophrenia, autism and hetero-aggression. These data reinforce the hypothesis for a link between genetically low LDL-C levels and psychiatric disorders.