Bone lesions in systemic mastocytosis: Bone histomorphometry and histopathological mechanisms.

Osteoporosis is considered the most frequent skeletal manifestation of systemic mastocytosis (SM). We performed a retrospective analysis of sixty patients (37 males and 23 females) who underwent a bone biopsy in the assessment of SM or in the assessment of unexplained bone fragility. Thirty-three had simultaneously a bone marrow biopsy with a Jamshidi's needle; this sample was used for immunohistochemical analysis (tryptase, c-KIT. CD20, VCAM-1). Bone biopsy was realized in 42 cases in the assessment of SM to provide histologic proof of the disease and in 18 cases in the assessment of unexplained bone fragility and surprisingly revealed a SM. An increased bone turnover was observed in patients with SM with elevated eroded surfaces, osteoclast number and bone formation rate. In addition to nodules of mast cells (MC), a high number of MC was directly apposed on the trabeculae, affixed on the osteoblasts or the lining cells. The VCAM-1 adhesion protein recognizing α4ß7 and α4ß1 integrins may be a candidate to explain this particular adherence. One third of the bone marrow biopsies did not exhibit MC nodules or MC infiltration and led to a false negative diagnosis for SM. SM can be discovered in the assessment of fracture or osteoporosis. Transiliac bone biopsy allows for the diagnosis of the disease more accurately than bone marrow biopsy; it also provides a histomorphometric analysis of bone remodeling.

Metaplastic woven bone in bone metastases: A Fourier-transform infrared analysis and imaging of bone quality (FTIR).

Most osteolytic tumors are in fact mixed and contain an osteoblastic component associated with the predominant osteolytic areas. This metaplastic woven bone is always evidenced by histological analysis even in the absence of radiological expression. Metaplastic bone formation reflects the activation of new osteoblasts coming from the stimulation of the dormant lining cells. Twelve patients with secondary metastases of the iliac crest evidenced by hot spots on a 99Tc-MBP san were diagnosed by histomorphometry on bone biopsies. Fourier Transformed InfraRed analysis and Imaging (FTIRI) was used on 4µm thick sections of undecalcified bone. The mineralization degree, carbonate substitution, crystallinity and the cross-links ratio of collagen (1660/1690cm-1 bands) were determined. The matrix characteristics were analyzed and imaged in the pre-existing residual bone and in the metaplastic woven bone in the vicinity of the tumor cells. FTIRI provided images of the phosphate, amide and combination of peak ratio after having selected the peaks of interest. In addition, the matrix properties can be measured and compared between the old and newly-formed bones. Woven bone appeared poorly calcified with a low phosphate/amide ratio (P=0.03) crystallinity (P<0.0001) and carbonate substitution (P=0.003). Collagen was less mature as evidenced by lower cross-links (P=0.01). Woven bone associated with bone metastasis appears poorly mineralized and rapidly elaborated by osteoblasts. The collagenous phase of the bone matrix has a low level of reticulation. FTIRI is a powerful tool to measure and visualize the various components of the bone matrix in human diseases.

Low-trauma fractures without osteoporosis.

In clinical practice, areal bone mineral density (aBMD) is usually measured using dual-energy X-ray absorptiometry (DXA) to assess bone status in patients with or without osteoporotic fracture. As BMD has a Gaussian distribution, it is difficult to define a cutoff for osteoporosis diagnosis. Based on epidemiological considerations, WHO defined a DXA-based osteoporosis diagnosis with a T-score <-2.5. However, the majority of individuals who have low-trauma fractures do not have osteoporosis with DXA (i.e., T-score <-2.5), and some of them have no decreased BMD at all. Some medical conditions (spondyloarthropathies, chronic kidney disease and mineral bone disorder, diabetes, obesity) or drugs (glucocorticoids, aromatase inhibitors) are more prone to cause fractures with subnormal BMD. In the situation of fragility fractures with subnormal or normal BMD, clinicians face a difficulty as almost all the pharmacologic treatments have proved their efficacy in patients with low BMD. However, some data are available in post hoc analyses in patients with T score >-2. Overall, in patients with a previous fragility fracture (especially vertebra or hip), treatments appear to be effective. Thus, the authors recommend treating some patients with a major fragility fracture even if areal BMD T score is above -2.5.

Osteoporosis in Stickler syndrome. A new family case with bone histology study.

The Stickler syndrome (SS) has been described as a "hereditary progressive arthro-ophtalmopathy" by Stickler in 1965, due to mutations on the collagen genes. Currently about 40 different genes have been identified which encode for at least 27 different collagens. The majority of mutations occur in the COL2A1 gene on chromosome 12q13 (SS type I). Mutations in COL11A1 are less frequent (SS type II). More recently, mutations in COL11A2 and in the COL9A1 gene have been reported with particular phenotypes. The main features of this autosomal inherited disease are ocular, auditory with orofacial abnormalities and early-onset osteoarthritis. We report the clinical presentation of an adult and his son, with a particular focus on the bone status of the father, radiography, bone densitometry and transiliac bone biopsy showing that he was suffering from osteoporosis. The lumbar bone mineral density was low with a Z-score at -2.9. Transiliac bone biopsy showed a dramatic decrease of trabecular bone volume (8.6%; Nl: 19.5±4.9%), thin trabeculae and a disorganized trabecular network. A slight increase of osteoid parameters was observed. Bone resorption was markedly increased with an excessive number of active (TRAcP+) osteoclasts. The cortical width was normal, but a slight increase of cortical porosity was found. Osteoporosis has been rarely described in the SS. It might be useful to systematically perform a bone densitometry in all patients with SS and to discuss the indication of a transiliac bone biopsy in severe cases.

Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway.

Fibrodysplasia ossificans progressiva is a very rare heritable disease characterized by a progressive heterotopic endochondal ossification, occurring in the first decade of life, and leading thereafter to a severe ankylosis of the spine, limbs and jaw, with a progressive and severe functional disability. To date the cause of the disease remains unknown and no medical treatment has been proved efficient. It has recently been shown that a recurrent mutation in activation domain of the activin-receptor IA (ACVR1), a BMP receptor, could lead to an abnormal signalling pathway of BMP-4 and contribute to the occurrence of the devastating lesions characteristic of the disease.

Synergy of local, regional, and systemic non-specific stressors for host defense against pathogens.

The immune brinksmanship conceptual model postulates that many of the non-specific stressful components of the acute-phase response (e.g. fever, loss of appetite, iron and zinc sequestration) are host-derived systemic stressors used with the "hope" that pathogens will be harmed relatively more than the host. The concept proposes that pathogens, needing to grow and replicate in order to invade their host, should be relatively more vulnerable to non-specific systemic stress than the host and its cells. However, the conceptual model acknowledges the risk to the host in that the gamble to induce systemic self-harming stress to harm pathogens may not pay off in the end. We developed an agent-based model of a simplified host having a local infection to evaluate the utility of non-specific stress, harming host and pathogen alike, for host defense. With our model, we explore the benefits and risks of self-harming strategies and confirm the immune brinksmanship concept of the potential of systemic stressors to be an effective but costly host defense. Further, we extend the concept by including in our model the effects of local and regional non-specific stressors at sites of infection as additional defenses. These include the locally hostile inflammatory environment and the stress of reduced perfusion in the infected region due to coagulation and vascular leakage. In our model, we found that completely non-specific stressors at the local, regional, and systemic levels can act synergistically in host defense.

Fracture incidence after 3 years of aromatase inhibitor therapy.

BACKGROUND: The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. PATIENTS AND METHODS: A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. RESULTS: Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. CONCLUSION: This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women.

High prevalence of vertebral fractures in women with breast cancer starting aromatase inhibitor therapy.

BACKGROUND: The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer, at the initiation of aromatase inhibitor therapy. PATIENTS AND METHODS: A prospective, transversal and clinical study was conducted. Each woman had an extensive medical history, a biological evaluation, a bone mineral density (BMD) measurement and spinal X-rays. RESULTS: Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study. Eighty-five percent of these women had a 25-OH vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a T-score < -2 at one of the three site measurements. Ninety-five women (19.1%) had a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays evaluation revealed that 20% of the women had at least one vertebral fracture. The presence of vertebral fracture was associated with nonvertebral fracture history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4] and with spine BMD (OR 1.4, 95% CI 1.1-1.7). The prevalence of vertebral fracture reached 62.9% in women with age above 70 years and femoral T-score < -2.5. CONCLUSION: Before starting aromatase inhibitor therapy for breast cancer, a large proportion of women had a vitamin D insufficiency and vertebral fractures.

Validation of the adherence evaluation of osteoporosis treatment (ADEOS) questionnaire for osteoporotic post-menopausal women.

SUMMARY: We developed and validated a specific 12-item questionnaire to evaluate adherence to oral antiresorptive medication by post-menopausal osteoporotic women in everyday practice. Over the following 9 months, an index of ≤16 was associated with an increase in the risk of treatment discontinuation of 1.69 and of 2.10 for new patients who had started treatment within the previous year. INTRODUCTION: Adherence to medication in osteoporosis is poor. The goal of this study was to develop and validate a disease-specific questionnaire to evaluate adherence to treatment of women with post-menopausal osteoporosis taking oral antiresorptive medication. METHODS: A prototype adherence questionnaire with 45 items developed from patient interview, literature review, and physician opinion was evaluated in a sample of 350 post-menopausal women with osteoporosis treated in primary care. Item responses were matched against scores on the Morisky Medication Adherence Scale (MMAS). The most discriminant items were retained in the final questionnaire. Concurrent and predictive validity were assessed. RESULTS: Twelve items were associated with MMAS score at a probability level of 0.05. These were retained in the final questionnaire which provided an adherence index ranging from 0 to 22. An index of ≥20 was associated with a high probability of persistence and an index ≤ 16 with a high probability of treatment discontinuation in the following 9 months. CONCLUSIONS: The ADEOS-12 is a simple patient-reported measure to determine adherence to osteoporosis treatments with good concurrent and discriminant validity. This is the first disease-specific adherence measure to have been developed for osteoporosis.

CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth.

BACKGROUND: Loss of CD9 expression has been correlated with a higher motility and metastatic potential of tumour cells originating from different organs. However, the mechanism underlying this loss is not yet understood. METHODS: We produced a truncated form of partner 1 of CD9 (CD9P-1), GS-168AT2, and developed a new monoclonal antibody directed towards the latter. We measured the expression of CD9 and CD9P-1 in human lung tumours (hLTs), and monitored the level of CD9 in NCI-H460, in vitro and in vivo, in the presence and absence of GS-168AT2. RESULTS: Loss of CD9 is inversely related to the expression of CD9P-1, which correlates with the metastatic status of hLT (n=55). In vitro, GS-168AT2 is rapidly internalised and degraded at both the membrane and cytoplasm of NCI-H460, and this correlates with the association of GS-168AT2 with both CD9 and CD81. Intraperitoneal injections of GS-168AT2 in NCI-H460-xenografted Nude mice led to drastic inhibition of tumour growth, as well as to the downregulation of CD9, but not of CD81, in the tumour core. CONCLUSION: These findings show for the first time that CD9P-1 expression positively correlates with the metastatic status of hLT, and that the upregulation of CD9P-1 expression could be one of the mechanisms underlying the loss of CD9 in solid tumours. Our study also reveals that, under certain conditions, loss of CD9 could be a tumour growth-limiting phenomenon rather than a tumour growth-promoting one.

A truncated form of CD9-partner 1 (CD9P-1), GS-168AT2, potently inhibits in vivo tumour-induced angiogenesis and tumour growth.

BACKGROUND: Tetraspanins are transmembrane proteins known to contribute to angiogenesis. CD9 partner-1 (CD9P-1/EWI-F), a glycosylated type 1 transmembrane immunoglobulin, is a member of the tetraspanin web, but its role in angiogenesis remains to be elucidated. METHODS: We measured the expression of CD9P-1 under angiogenic and angiostatic conditions, and the influence of its knockdown onto capillary structures formation by human endothelial cells (hECs). A truncated form of CDP-1, GS-168AT2, was produced and challenged vs hEC proliferation, migration and capillaries' formation. Its association with CD9P-1, CD9, CD81 and CD151 and the expressions of these later at hEC surface were analysed. Finally, its effects onto in vivo tumour-induced angiogenesis and tumour growth were investigated. RESULTS: Vascular endothelial growth factor (VEGF)-induced capillary tube-like formation was inhibited by tumour necrosis factor α and was associated with a rise in CD9P-1 mRNA expression (P<0.05); accordingly, knockdown of CD9P-1 inhibited VEGF-dependent in vitro angiogenesis. GS-168AT2 dose-dependently inhibited in vitro angiogenesis, hEC migration and proliferation (P<0.05). Co-precipitation experiments suggest that GS-168AT2 corresponds to the sequence by which CD9P-1 physiologically associates with CD81. GS-168AT2 induced the depletion of CD151, CD9 and CD9P-1 from hEC surface, correlating with GS-168AT2 degradation. Finally, in vivo injections of GS-168AT2 inhibited tumour-associated angiogenesis by 53.4±9.5% (P=0.03), and reduced tumour growth of Calu 6 tumour xenografts by 73.9±16.4% (P=0.007) without bodyweight loss. CONCLUSION: The truncated form of CD9P-1, GS-168AT2, potently inhibits angiogenesis and cell migration by at least the downregulation of CD151 and CD9, which provides the first evidences for the central role of CD9P-1 in tumour-associated angiogenesis and tumour growth.

New laboratory tools in the assessment of bone quality.

Bone quality is a complex set of intricated and interdependent factors that influence bone strength. A number of methods have emerged to measure bone quality, taking into account the organic or the mineral phase of the bone matrix, in the laboratory. Bone quality is a complex set of different factors that are interdependent. The bone matrix organization can be described at five different levels of anatomical organization: nature (organic and mineral), texture (woven or lamellar), structure (osteons in the cortices and arch-like packets in trabecular bone), microarchitecture, and macroarchitecture. Any change in one of these levels can alter bone quality. An altered bone remodeling can affect bone quality by influencing one or more of these factors. We have reviewed here the main methods that can be used in the laboratory to explore bone quality on bone samples. Bone remodeling can be evaluated by histomorphometry; microarchitecture is explored in 2D on histological sections and in 3D by microCT or synchrotron. Microradiography and scanning electron microscopy in the backscattered electron mode can measure the mineral distribution; Raman and Fourier-transformed infra-red spectroscopy and imaging can simultaneously explore the organic and mineral phase of the matrix on multispectral images; scanning acoustic microscopy and nanoindentation provide biomechanical information on individual trabeculae. Finally, some histological methods (polarization, surface staining, fluorescence, osteocyte staining) may also be of interest in the understanding of quality as a component of bone fragility. A growing number of laboratory techniques are now available. Some of them have been described many years ago and can find a new youth; others having benefited from improvements in physical and computer techniques are now available.

Impact of hypovitaminosis D and alfacalcidol therapy on survival of hemodialysis patients: results from the French ARNOS study.

BACKGROUND: In chronic kidney disease and dialysis patients, vitamin D deficiency is associated with mortality. In some observational studies, calcitriol analogue therapy was associated with a better survival rate in hemodialysis (HD) patients. The aim of this study was to determine the relationship between serum 25-hydroxyvitamin D (25-OHD) levels and alfacalcidol therapy with HD patients' outcomes. METHODS: We measured baseline 25-OHD levels using a cross-sectional analysis in 648 HD prevalent patients from the regional ARNOS French cohort. A 42-month survival analysis was applied according to serum 25-OHD level and calcitriol analogue therapy. RESULTS: The prevalence of 25-OHD insufficiency <30 ng/ml was high (73%), with only 22% taking native vitamin D supplementation. A baseline 25-OHD level above the median value (18 ng/ml) was associated with lower all-cause mortality [hazard ratio (HR), 0.73 (0.5-0.96); p = 0.02] after adjustment for age, gender, dialysis vintage, calcemia, phosphatemia, cardiovascular disease, and diabetes. Only in monovariate analysis was low-dose oral alfacalcidol therapy associated with a better survival rate in patients with and without 25-OHD deficiency [HR, 0.7 (0.5-0.92); p = 0.05]. CONCLUSIONS: Our study shows that, among prevalent HD patients, low 25-OHD levels affect mortality. Alfacalcidol therapy, especially in small doses, may provide compensation, but this needs to be further confirmed using prospective controlled studies comparing native and active vitamin D compounds.

Association between very low PTH levels and poor survival rates in haemodialysis patients: results from the French ARNOS cohort.

INTRODUCTION: A very low parathyroid hormone (PTH) level (VLPL) is associated with an increased risk of adynamic bone disease, vascular calcification, and mortality in haemodialysis (HD) patients. The aim of the study was to assess the frequency, the associated factors, and the prognosis of non-surgical VLPL in a cohort of prevalent HD patients. METHODS: In July 2005, a cross-sectional study was performed on the French ARNOS cohort in 1,348 prevalent HD patients from 24 dialysis centres in the Rhône-Alpes area. Patients with a baseline intact PTH level <50 pg/ml (VLPL, Group 1) and ≥ 50 pg/ml (Group 2) were compared and a 42-month survival analysis was performed. Patients with prevalent or incident parathyroidectomy were excluded. RESULTS: We studied 1,138 prevalent HD patients. As compared to patients of Group 2 (n = 1,019), patients with VLPL (Group 1, n = 119) had lower serum albumin levels (34.5 ± 5 vs. 36.4 ± 5 g/l, p < 0.0001), less protein intake (nPCR 0.99 ± 0.28 vs. 1.1 ± 0.28 g/kg/day, p = 0.01), higher calcaemia (2.30 ± 0.2 vs. 2.26 ± 0.2 mmol/l, p = 0.01) and were more frequently treated with calcium carbonate (67 vs. 54%, p < 0.001). Patients with VLPL had a higher mortality rate (HR: 1.4 (1.07-1.8), p = 0.006) after adjustment for age, gender, diabetes, and dialysis vintage. The odds ratios of mortality for patients with VLPL remained higher in all calcaemia and serum albumin quartiles. Only 3/119 patients in Group 1 did not receive any PTH-lowering therapies (i.e. calcium carbonate (67%), alfacalcidol (38%), cinacalcet (10.1%), and dialysate calcium ≥ 1.5 mmol/l (94%)). CONCLUSION: In this observational French cohort, VLPL was observed in 10% of prevalent HD patients and was associated with poor survival rates. An inadequate therapeutic strategy could be responsible for this observation. The real consequences of this iatrogenic adynamic bone disease remain hypothetical, but it may be related to the risk of developing vascular calcification. It is hypothesized that a more adequate strategy, using fewer PTH-lowering therapies in cases of VLPL, may help in improving the poor prognosis.

Bone metastasis: histological changes and pathophysiological mechanisms in osteolytic or osteosclerotic localizations. A review.

The development of a bone metastasis involves interactions between the tumor cells, the bone marrow microenvironment and the bone cells themselves. A better understanding of the pathophysiological changes occurring in bone metastasis can be obtained from histopathological examination of invaded specimens. This review focuses on the main molecular mechanisms implied in the localization and growth of malignant cells in the bone marrow. The corresponding histologic developmental stages are illustrated both in osteolytic (or mixed metastasis) or in the osteosclerotic forms by histological analysis, immunohistochemistry and microcomputed tomographic analysis of bone samples. In both cases, the malignant cells find a "fertile soil" in the bone marrow microenvironment. They use the growth factors released by bone cells for the coupling between osteoclasts/osteoblasts to promote their own development. In turn, they elaborate a variety of cytokines that can promote osteoclastogenesis (PTHrP, IL-1, IL-6…) or on the contrary, other growth factors that can boost the osteoblastic activity (ET1, IGFs). A "vicious circle" occurs between the malignant cells and the bone cells leading to the radiological expression of the metastasis.

GLP-2 administration in ovariectomized mice enhances collagen maturity but did not improve bone strength.

Osteoporosis and bone fragility are progressing worldwide. Previous published literature reported a possible beneficial role of gut hormones, and especially glucagon-like peptide-2 (GLP-2), in modulating bone remodeling. As now (Gly2)GLP-2 is approved in the treatment of short bowel syndrome, we thought to investigate whether such molecule could be beneficial in bone fragility. MC3T3 and Raw 264.7 were cultured in presence of ascending concentrations of (Gly2)GLP-2. Collagen crosslinks, maturity, lysyl oxidase activity and osteoclastogenesis were then analyzed. Furthermore, (Gly2)GLP-2, at the clinical approved dose of 50 µg/kg/day, was also administered to ovariectomized Balb/c mice for 8 weeks. Hundred µg/kg zoledronic acid (once iv) was also used as a positive comparator. Bone strength, microarchitectures and bone tissue composition were analyzed by 3-point bending, compression test, microCT and Fourier transform infrared imaging, respectively. In vitro, (Gly2)GLP-2 was potent in enhancing bone matrix gene expression but also to dose-dependently enhanced collagen maturation and post-processing. (Gly2)GLP-2 was also capable of reducing dose-dependently the number of newly generated osteoclasts. However, in vivo, (Gly2)GLP-2 was not capable of improving neither bone strength, at the femur diaphysis or lumbar vertebrae, nor bone microarchitecture. On the other hand, at the tissue material level, (Gly2)GLP-2 significantly enhances collagen maturity and reduce phosphate/amide ratio. Overall, this study highlights that despite modification of bone tissue composition, (Gly2)GLP-2, at the clinical approved dose of 50 µg/kg/day, did not provide real beneficial effects in improving bone strength in a mouse model of bone fragility. Further studies are recommended to validate the best dose and regimen of administration to significantly enhance bone strength.

Can postoperative calcemia kinetics predict the risk of hypocalcemia for the management of parathyroid adenoma in ambulatory surgery?

INTRODUCTION: The goal of this study was to analyse the kinetics of corrected calcemia levels (Cac) after parathyroid excision and to determine the percentage of variation (ΔCa) in the initial hours after surgery, in order to entertain an early discharge. POPULATION AND METHODS: Were included in this study, patients undergoing operation for parathyroid adenoma responsible for primary hyperparathyroidism (PHP). The Cac was measure preoperatively and four hours after surgery, and then every day until patient discharge. Group A included patients for whom the Cac was inferior to 2.2mmol/L at least once postoperatively while group B included patients for whom the Cac was always equal or superior to 2.2mmol/L. The ΔCa represented the percentage of the fall in postoperative Cac with respect to preoperative Cac. RESULTS: Between 2010 and 2017, 156 patients fulfilled the inclusion criteria (women 80.8%, [sex ratio 1:4], median age 64 years old). Preoperative Cac was statistically significantly lower in group A compared to group B (2.67 vs. 2.82mmol/L; P<0.0001). In total, 9.6% of patients had calcium supplementation for hypocalcemia, symptomatic or not. Postoperative Cac reached its nadir value on postoperative day 2. At four hours postoperative, the risk of postoperative calcelmia falling below 2.2mmol/L appeared when the ΔCa was superior to 6% with a sensitivity of 92.9% and a negative predictive value of 97.4%. CONCLUSION: After excision of a parathyroid adenoma for PHP, the Cac falls rapidly and reaches its nadir value on day 2. If the fall in calcemia is less than 6% four hours after surgery (vs. preoperative level), early discharge within the framework of ambulatory surgery is possible.

[Importance of a regional observatory of malarial chemoresistance, an emerging public health problem in the Guyanas region]. / Intérêt d'un observatoire régional de la chimiorésistance du paludisme, problème émergent de santé publique dans la région des Guyanes.

A regular implementation of prophylactic and therapeutic decision trees was organized on a consensus basis in Cayenne, French Guiana in 1990, 1995 and 2002. The updated recommendations were based on the knowledge of the in vitro chemosensitivity profiles of the local isolates, mainly coming from big rivers (Maroni and Oyapock, frontiers with Suriname and Brazil, respectively; and more recently Approuague). Most of the patients infected by Plasmodium falciparum were followed by the medical staff of the main hospitals (Cayenne and Saint-Laurent) and of the peripheral health centers in remote areas. Consequently the epidemiological situation and evolution of chemoresistance have been widely observed on a long-term (since 1994) basis in the Maroni region. Yet, we have only partial information coming from the Oyapock valley, even though an important (most of the time) illegal immigration has been developing since the 90s' leading to a notable modification of the epidemiological status of malaria in this eastern region, including a regular increase of P. vivax infections. Presently very little P. vivax chloroquine (and mefloquine) resistance has been identified but this result could lead to a real public health problem in a near future. As such, the National Reference Center on Plasmodium Chemoresistance in the French West Indies and Guiana (CNRCP-AG in French) is a unique observatory of malaria chemoresistance in the Guyanese shield which works with research laboratories of the Institut Pasteur, Paris. This network strategy offers a very attractive perspective for applications of modern tools, including the validation of chemoresistance molecular markers, for malaria control at both medical and public health levels. Some examples related to chloroquine and artemether resistance are given.