SATB2-associated syndrome: characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients.

BACKGROUND: Individuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density. RESULTS: Digitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%). CONCLUSION: We conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS).

Increased expression of fibroblast growth factor 23 is the signature of a deteriorated Ca/P balance in ageing laying hens.

The present study concerned the effect of ageing in laying hens, from 23 to 90 weeks of age, on the regulation of Ca metabolism related to the requirement for eggshell mineralization. Samples were collected from parathyroid gland (PG), liver, jejunum, medullary bone (MB) and kidney for a quantitative study of candidate gene expression. Although parathyroid hormone (PTH) gene expression in the PG did not vary with age, a stronger challenge to Ca homeostasis was suggested in aged hens. Indeed gene expression of Ca transporters , Vitamin D Receptor (VDR) in the jejunum, and that of transient receptor potential channel subfamily V member 5 (TRPV5) in the kidney decreased. This could exacerbate bone resorption and impair bone accretion, as attested by a higher expression of the Carbonic Anhydrase 2 (CA2) gene and a lower expression of collagen type I alpha 1 chain (COL1A1) in the MB. The increased expression of Fibroblast Growth Factor 23 (FGF23) in the MB likely contributed to the decreased plasma levels of 1.25(OH)2D3 and the altered expression of target genes under its regulation. Our data highlights the molecular mechanisms underlying the osteoporotic syndrome previously documented in aged laying hens, thus providing new perspectives for future interventions.

Possible roles of parathyroid hormone, 1.25(OH)2D3, and fibroblast growth factor 23 on genes controlling calcium metabolism across different tissues of the laying hen.

This study provides an integrative description of candidate gene expression across tissues involved in calcium (Ca) metabolism during the egg laying cycle, using the well-defined model of Ca supply as fine or coarse particles of calcium carbonate (CaCO3). Plasma and tissue samples were collected from hens at the peak of laying at 0 to 1, 9 to 10, and 18 to 19 h postovulation (PO). After mRNA preparation from the parathyroid gland, medullary bone, liver, kidney, duodenum, and jejunum, gene expressions were quantified using RT-qPCR. The highest levels of parathyroid hormone (PTH) mRNA in the parathyroid gland (P < 0.05), and of the active form of vitamin D3 1.25(OH)2D3 in the plasma (P < 0.01) were observed at 18 to 19 h PO. During this active phase of eggshell formation, bone resorption was attested to high levels of plasma inorganic phosphorus (iP) and the receptor activation of nuclear factor-κB expression in the bone (P < 0.001 and P < 0.05, respectively). At this stage, 5 genes of the transcellular and the paracellular Ca absorption pathways in the intestine (P < 0.05) and the Ca channel transient receptor potential cation channel subfamily V member 5 (P < 0.05), involved in its reabsorption in the kidney, were overexpressed. At 0 to 1 h PO during the subsequent daylight period, 2 candidates of the transcellular and the paracellular Ca pathways (P < 0.05) remained at high levels in the intestine, while calbindin D 28K expression was the highest in the kidney (P < 0.05). As PTH mRNA and 1.25(OH)2D3 were low, bone accretion was likely active at this stage. The phosphaturic hormone fibroblast growth factor 23 (FGF23) was overexpressed at 18 to 19 h PO (P < 0.05) in the bone when plasma iP was high, which suggested a role in the subsequent reduction of P reabsorption in the kidney, as attested to the decreased expression of P cotransporters, leading to iP clearance from the plasma at 0 to 1 h PO (P < 0.05). The low levels of 1.25(OH)2D3 at this stage coincided with increased expression of the 24-hydroxylase gene in the kidney (P < 0.05). In hens fed fine particles of CaCO3, higher plasma levels of 1,25(OH)2D3 and higher expression of several genes involved in bone turnover reflected a stronger challenge to Ca homeostasis. Altogether, these data support the hypothesis that FGF23 could drive vitamin D metabolism in the laying hen, as previously documented in other species and explain the tight link between P and Ca metabolisms.

Candidate genes of the transcellular and paracellular calcium absorption pathways in the small intestine of laying hens.

To meet the high calcium (Ca) demand during eggshell biomineralization (2 g of Ca per egg), laying hens develop specific metabolic regulations to maintain Ca homeostasis. The intake of Ca, its solubilization, and absorption capacity are enhanced at sexual maturity (SM). A better knowledge of the intestinal Ca transporters involved in their variations at this stage could indicate new nutritional strategies to enhance Ca digestive utilization. Transcellular Ca absorption pathway and its major player calbindin-D 28 K (CALB1) mediate a saturable transport, which has been extensively described in this model. Conversely, a contribution by the paracellular pathway involving non-saturable Ca transport through intercellular tight junction has also been suggested. The aim of the present study was to identify candidate genes of these two pathways and their patterns of expression, in immature pullets (12, 15, and 17 wk old) and mature laying hens (23 wk old) in the duodenum, jejunum, and ileum. Using RT-qPCR, this study identifies 3 new candidate genes for transcellular, and 9 for paracellular Ca transport. A total of 5 candidates of the transcellular pathway, transient receptor potential cation channels subfamily C member 1 (TRPC1) and M member 7 (TRPM7); CALB1 and ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) and ATPase plasma membrane Ca2+ transporting 2 (ATP2B2) were enhanced with age or after SM in the duodenum, the jejunum or all 3 segments. A total of 4 candidates of the paracellular pathway Claudin 2 (CLDN2) and tight junction proteins 1, 2, and 3 (TJP1, TJP2 and TJP3) increased in the small intestine after SM. Additionally, CALB1, ATP2B2, and CLDN2 were overexpressed in the duodenum or the jejunum or both segments after SM. The enhanced expression of candidate genes of the paracellular Ca pathway after SM, supports that the non-saturable transport could be a mechanism of great importance when high concentrations of soluble Ca are observed in the intestinal content during eggshell formation. Both pathways may work cooperatively in the duodenum and jejunum, the main sites of Ca absorption in laying hens.

How the reference values for serum parathyroid hormone concentration are (or should be) established?

Well-validated reference values are necessary for a correct interpretation of a serum PTH concentration. Establishing PTH reference values needs recruiting a large reference population. Exclusion criteria for this population can be defined as any situation possibly inducing an increase or a decrease in PTH concentration. As recommended in the recent guidelines on the diagnosis and management of asymptomatic primary hyperparathyroidism, PTH reference values should be established in vitamin D-replete subjects with a normal renal function with possible stratification according to various factors such as age, gender, menopausal status, body mass index, and race. A consensus about analytical/pre-analytical aspects of PTH measurement is also needed with special emphasis on the nature of the sample (plasma or serum), the time and the fasting/non-fasting status of the blood sample. Our opinion is that blood sample for PTH measurement should be obtained in the morning after an overnight fast. Furthermore, despite longer stability of the PTH molecule in EDTA plasma, we prefer serum as it allows to measure calcium, a prerequisite for a correct interpretation of a PTH concentration, on the same sample. Once a consensus is reached, we believe an important international multicentre work should be performed to recruit a very extensive reference population of apparently healthy vitamin D-replete subjects with a normal renal function in order to establish the PTH normative data. Due to the huge inter-method variability in PTH measurement, a sufficient quantity of blood sample should be obtained to allow measurement with as many PTH kits as possible.

[Assessment of a multidisciplinary care for 169 excised women with an initial reconstructive surgery project]. / Évaluation d'une prise en charge multidisciplinaire chez 169 patientes excisées demandeuses d'une chirurgie réparatrice.

OBJECTIVE: To assess the benefits of a multidisciplinary care among excised women with an initial surgery project and identify the reasons for discarding surgery. METHODS: Descriptive and retrospective study performed between the 1st of January 2006 and the 31st of December 2011 at the Armand Trousseau Hospital, Paris. All excised patients went through consultations with a mid-wife, a sexologist, a psychologist, a gynaecologist-obstetrician and, for some of them, underwent a clitoral reconstructive surgery. RESULTS: One hundred and sixty-nine patients were included: among them, 61 patients (36%) were operated and 108 patients (64%) have given spontaneously to surgery, 32% being reinforced by consultation. Ninety-one on 111 patients (82%) respondents were satisfied with their care pathway. The main motivation was to support identity for 39 patients operated (64%) while improving sex prevailed for 56 non-operated patients (52%). The study evidenced an improvement of the functional and sexual life quality after surgery: 17% experienced an orgasm versus 2% before surgery, 56% reported an increase in their libido and 41% a decrease in dyspareunia. CONCLUSION: Clitoral reconstructive surgery with multidisciplinary care tends to improve the functional and sexual life quality of excised patients, though it is not always necessary. Some of the patients discard their initial project of reconstructive surgery as in some of the cases, a multidisciplinary care only seems sufficient.

[Giant retroperitoneal hematoma in the peripartum of a normal delivery, "expectative attitude"]. / Hématome rétropéritonéal géant péripartum d'un accouchement normal, "expectative attitude".

We describe a case involving spontaneous retroperitoneal hematoma complicating a normal delivery in a context of a Disseminated Intravascular Coagulation (DIVC) at the end of the pregnancy. Given the defaced symptomatology, an abdomino-pelvic scanner and an examination with a general anaesthesia made it possible to diagnose and to monitor the hematoma in intensive care. The correction of the hemostasis troubles and of the anemia, without another invasive intervention, allowed a return to home at the eighth day. The pathophysiological mechanisms underlying development and practicable treatments of this post-partum hematoma are discussed.

[Surgical management of intrauterine adhesions: is benefice bigger than risk?]. / Synéchie utérine: le jeu chirurgical en vaut-il la chandelle?

Management of intrauterine synechiae in a context of infertility remains a challenge, in spite of hysteroscopic microsurgery progress. There is no published prospective study to be used as a guideline. Anatomic, but most of all functional prognosis are directly correlated to the severity of adhesions and the number of surgical procedures required to complete treatment. Complications during surgery are not infrequent, but are well known and often benign. Obstetrical complications are much less frequent but often severe (abnormal placentation, uterine rupture). Recurrences are common enough to impose a systematic second-look diagnostic hysteroscopy. However, the benefit gained by the recovery of fertility (either spontaneous or not) remains superior, in my opinion, to the risks of the surgical management.

[How does peritoneal fluid flow influence anatomical distribution of endometriotic lesions?]. / Etude de la distribution anatomique des lésions endométriosiques: un argument majeur en faveur de la participation de la théorie de la régurgitation dans la physiopathologie de l'endométriose.

Endometriosis is a common disease in gynecology. Many theories were proposed to explain the endometriosis pathogenesis. The distribution of the endometriosis lesions seems to be interesting in order to understand the endometriosis pathogenesis. This distribution is asymmetric. This asymmetric distribution of endometriosis is explained by the anatomy of the peritoneal cavity and by the intraperitoneal fluids. It strongly confirms the role of menstrual regurgitation and peritoneal fluid in the endometriosis genesis. The similar asymmetric distribution for all types of endometriosis (superficial lesions, ovarian endometriosis cyst, deep endometriosis) is an argument in favor of a unique origin for the different types of lesions.

Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter.

OBJECTIVES: To determine whether sonography can be used to distinguish hyperthyroidism from hypothyroidism in pregnancies with fetal goiter. METHODS: This was a retrospective study of 39 cases of fetal goiter. The majority of the mothers had Graves' disease. Fetuses were scanned for the existence of a hypertrophic thyroid gland (goiter) beginning at 22 gestational weeks. Once a goiter was diagnosed, different echographic features were analyzed and the effect of chosen treatment on fetal thyroid development was monitored. RESULTS: On color Doppler, 68.8% of hypothyroid goiters had a peripheral vascular pattern vs. 20% in cases of fetal hyperthyroidism (P = 0.0574). No hypothyroid goiter presented central vascularization whereas half the hyperthyroid goiters did (P = 0.0013). Fetal tachycardia was a good indicator of hyperthyroidism (57.1% v.s 6.3%; P = 0.0055). Delayed bone maturation was seen in hypothyroid goiters (46.9% vs. 0%; P = 0.0307), while advanced bone maturity was specific to hyperthyroid goiters (85.7% vs. 0%; P < 0.0001). Lastly, an increase in fetal movement was observed in cases of fetal hypothyroidism (43.8% vs. 0%; P = 0.0364). CONCLUSION: Based on the color Doppler pattern of goiter, fetal heart rate, bone maturation and fetal mobility, we established an ultrasound score to predict fetal thyroid function in cases of fetal goiter.

[The role of biology in the diagnosis of cerebrospinal fluid leaks]. / Place de la biologie dans la prise en charge des brèches ostéoméningées.

Cerebrospinal fluid leakage is a rare but critical condition with a substantial risk of intracranial infection, therefore its diagnosis and treatment is of major importance. CSF leakage diagnostic can be a challenging problem. Nephelometric measurement of beta-trace protein in the liquorrhoea is a non-invasive and fast method that can be used for CSF leakage diagnosis. It should kept in mind, however, that the cut-off of 1.1 mg/L is not suitable for patients with bacterial meningitis and those with a reduced glomerular filtration rate. Complementary use of beta-trace protein assay and beta2-transferrin detection is therefore recommended.

[Bladder endometriosis and barrenness: diagnostic and treatment strategy]. / Endométriose vésicale et infertilité: modalités de prise en charge diagnostique et thérapeutique.

Deep infiltrating endometriosis is a well-known female disease responsible for chronic pelvic pain, urinary dysfunction, infertility, and altered quality of life. Endometriosis and infertility are complex entities and the optimal choice of management of both of them remains obscure. Mechanism of development of the disease has to be understood to optimize patients care. The link between barrenness and endometriosis is well known, but there is no direct link between bladder lesion and infertility. Bladder endometriosis is a deeply infiltrating endometriosis lesion. Its management is first diagnostic and then remedial. In case of ineffectiveness of medical strategy, surgical treatment is indicated. However, for patient suffering from symptomatic isolated bladder endometriosis, surgical management can be offered in first intention. Isolated bladder injuries due to endometriosis are mostly treated by conservative laparoscopic surgery, after a complete evaluation of endometriosis disease and barrenness by clinical exam and imaging techniques.

[Assessment of the urinary side effects after surgery for deep pelvic endometriosis]. / Evaluation des troubles urinaires après chirurgie de l'endométriose profonde.

OBJECTIVE: To evaluate the urinary side effects after laparoscopic surgery for deep endometriosis. PATIENTS AND METHOD: Longitudinal study including 86 patients operated for deep pelvic endometriosis : 58 (68%) with colorectal endometriosis, 21 (24%) with utero-sacral ligament endometriosis and 7 (8%) with recto-vaginal septum endometriosis. Assessment of the urinary side effects was permormed using the Bristole Female Lower Urinary Tract Symptom questionnaire. RESULTS: On postsurgical follow-up, almost all patients described: hesistancy (p = 0.02), strain to start (p = 0.04), stopping flow (p = 0.01), incomplete emptying (p = 0.008) and reduce stream (p=0.02). Only patients who had resection of both utero-sacral ligaments had significative postsurgical urinary dysfunction with stopping flow (p = 0.02) and incomplete emptying (p = 0.004). Patients with colorectal resection had also significative postsurgical urinary dysfunction with hesitancy (p = 0.02), strain to start (p = 0.03), stopping flow (p = 0.007) and incomplete emptying (p = 0.004). In patients with rectal resection, urinary dysfunctions are raised when rectal resection is associated to resection of both utero-sacral ligaments. CONCLUSION: Postoperatively, urinary side effects occurred only in patients with segmental colorectal endometriosis resection associated with bilateral utero-sacral ligament resection. Sparing nerve surgery of the pelvic nerves, can reduce these urinary side effects.

Uterine compression sutures for postpartum bleeding with uterine atony.

OBJECTIVE: To assess the efficacy of a new uterine compression suturing technique in reducing postpartum haemorrhage secondary to severe uterine atony. DESIGN: Retrospective study. SETTING: University hospital between December 2000 and March 2006. POPULATION: Twenty women with uterine atony and postpartum bleeding that did not react to usual medical management. METHODS: All these women underwent compression suturing of the uterus, in which the anterior and posterior walls of the uterus were attached so as to compress the uterus. MAIN OUTCOME MEASURES: Arrest of the bleeding, complications and fertility. RESULTS: Uterine compression suturing was sufficient to stop the bleeding immediately in 95% of the women. None of the women developed complications related to the procedure. All the women recovered normal menstrual cycles. Since uterine compression suturing, eight women have tried to conceive and six (75%) have had a term delivery. CONCLUSION: Uterine compression suturing is a simple conservative procedure to stop postpartum haemorrhage in the case of failure of the usual management. This surgical technique can be performed quickly and does not seem to decrease fertility.

[Bilateral amyotrophic neuralgia (Parsonage Turner syndrome) with HIV seroconversion]. / Névralgie amyotrophiante (syndrome de Parsonage-Turner) bilatérale révélatrice d'une séroconversion VIH.

We report a unusual case of neuralgic amyotrophy (NA) occurring during the seroconversion stage of an HIV infection. Combined with previously published cases, our observation suggests that NA associated with HIV could belong to the group of early multiplex mononeuritis. Neurologists should be aware of HIV infection when managing a patient with NA.

Clinical comparison of three labeled-antibody immunoassays of free triiodothyronine.

Three labeled-antibody immunoassays of free triiodothyronine (FT3) were studied in hyperthyroid patients, patients with nonthyroidal illness, and patients being treated with amiodarone; we also studied sera presenting known interferences (n for all groups = 465). The results were compared with those of a one-step labeled-analog assay. The precision of the two automated assays were similar to that of the manual assays. The three labeled-antibody FT3 assays demonstrated a satisfactory diagnostic performance for confirming hyperthyroidism and robustness to interference; nevertheless, two assays displayed unusual behavior in some patients with nonthyroidal illness, with chronic renal failure, or after amiodarone therapy.

Sensitive assay of thyroid stimulating hormone in depressed patients.

A decreased thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) has been noted in major depression. Some authors found a positive correlation between baseline TSH levels and TSH response to TRH, especially with sensitive assays of TSH. Serum TSH was assayed by a sensitive method in 55 depressed patients and 38 healthy volunteers. Patients were subclassified according to DSM-III as suffering from major depression (n = 40) and non-major depression (n = 15). The patients' mean score on the Hamilton Rating Scale for Depression (HRSD) was 50 (SD = 10). The TSH value was significantly lower in depressed patients compared with healthy control subjects, and in major compared with non-major depression. No differences in TSH levels distinguished the various subtypes of major depression. There was a significant negative correlation between global HRSD scores and TSH concentrations. The most anxious patients tended to have significantly lower TSH values compared with the least anxious subjects. Total HRSD insomnia scores correlated negatively with TSH concentrations after log transformation. The sensitive determination of TSH may also provide an index of thyroid function in depression that is simpler to implement than measurements of the TSH response to TRH.

Hypersecretion of melatonin following diurnal exposure to bright light in seasonal affective disorder: preliminary results.

Night-time melatonin secretion was measured in five depressed inpatients with seasonal affective disorder before and after 1-week of morning and evening exposure to bright (3000 lux) and dim (300 lux) light. Analysis of variance by ranks showed no differences in timing of melatonin secretion but statistically significant differences in plasma melatonin levels. There was a decrease of the area under the curve after bright light and a very robust rebound after exposure to dim light. The failure to constitute a parallel group of patients in a crossover design did not permit to control for an ordering effect of light exposure. These findings raise many questions concerning the diurnal sensitivity to different intensities of light in seasonal affective disorder.