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Background: The complexity of the hospital-city care pathway is a real challenge because of the lack of coordination and communication between many stakeholders. As part of a call for projects from the General Directorate of Healthcare Provision, an experiment involving private oncology coordinating nurses was developed to address this issue. To our knowledge, there is no evaluation so far of such a protocol ., Methods: This single-center retrospective study focused on data from the ONC'IDEC program between 2015 and 2018, where 28 private nurses provided a 24/7 hotline. The objective was to qualitatively assess the coordination of this system. The nature and number of calls, patient satisfaction and medico-economic parameters were assessed., Results: More than a hundred patients (n=114) were included in this device (mean age: 72 ± 12 years). The most frequent reasons for calls concerned the patient's general condition (35 %) and home treatment follow-ups (13 %) but also referrals to the primary doctor (4 %), which helped avoiding hospitalizations. The patients were satisfied with the experiment (overall score of 8.4/10)., Discussion: Thanks to the ONC'IDEC program, patients were able to benefit from more appropriate care through a privileged interlocutor by making their care pathway more fluid and avoiding hospitalizations. It would be interesting to confirm these results by means of a study with a higher level of evidence, by comparing this protocol to conventional hospital coordination., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA 2 ). Here we investigated the potential of a novel DOTHA 2 -conjugated, 64 Cu-radiolabeled GRPR peptide antagonist, [D-Phe 6 -Sta 13 -Leu 14 -NH 2 ]bombesin(6-14) (DOTHA 2 -PEG-RM26) to visualize prostate tumors by PET imaging., Methods: DOTHA 2 -PEG-RM26 was conveniently and efficiently assembled on solid support. The compound was radiolabeled with 64 Cu and its affinity, stability, cellular uptake on PC3 prostate cancer cells were evaluated. The in vitro and in vivo behavior of [ 64 Cu]DOTHA 2 -PEG-RM26 was examined by PET imaging using human PC3 prostate cancer xenografts and its behavior was compared to that of the analogous [ 64 Cu]NOTA-PEG-RM26., Results: The inhibition constant of nat Cu-DOTHA 2 -PEG-RM26 was in the low nanomolar range (0.68±0.19 nM). The [ 64 Cu]DOTHA 2 -PEG-RM26 conjugate was prepared with a labeling yield >95% and molar activity of 56±3 GBq/μmol after a 5-min room temperature labeling. [ 64 Cu]-DOTHA 2 -PEG-RM26 demonstrated rapid blood and renal clearance as well as a high tumor uptake. Small animal PET images confirmed high and specific uptake in PC3 tumor. Both [ 64 Cu]-DOTHA 2 -PEG-RM26 and [ 64 Cu]-NOTA-PEG-RM26 displayed similar tumor and normal tissue uptakes at early time point post injection., Conclusions: [ 64 Cu]-DOTHA 2 -PEG-RM26 allows visualization of prostate tumors by PET imaging. DOTHA 2 enables fast 64 Cu chelation under mild condition, and as such could be used advantageously for the development of other 64 Cu-labeled peptide-derived PET tracers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Breast cancer is the most frequent and deadly malignancy in women worldwide. Despite national screening programs combined with new treatments relapse rate remain high and new therapies are needed. From previous work, we identified PACE4, a member of the proprotein convertase (PCs) family of endoproteases, as a novel therapeutic target in prostate cancer. In the present study we asked the question if PACE4 could also be a potential target in breast cancer. In clinical samples of breast adenocarcinoma, we observed a specific overexpression of PACE4 in the estrogen-receptor (ER) positive subtype. We therefore looked for a breast cancer cell line model which would be representative and thus focused on the ZR-75-1 since it both expresses PACE4 and is estrogen-receptor positive. We compared stable knockdowns of furin, PACE4 and PC7 in the estrogen-receptor-positive cell line ZR-75-1 to evaluate their respective contribution to cell growth and tumor progression. PACE4 was the only PC displaying an impact on cell growth. A PACE4 peptide-based inhibitor (C23) was tested and shown to decrease proliferation of ZR-75-1 cells in cell based assays. C23 also had potent effects of tumor progression in vivo on xenografts of the ZR-75-1 cell line in athymic nude mice. Thus, PACE4-silencing and systemic administration of a PACE4 inhibitor resulted in hindered tumor progression with reduction in proliferative indices and increased cell quiescence assessed with biomarkers. Our results suggest that PACE4 is a promising target for estrogen-receptor-positive breast cancer., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

The potential of PACE4 as a pharmacological target in prostate cancer has been demonstrated as this proprotein convertase is strongly overexpressed in human prostate cancer tissues and its inhibition, using molecular or pharmacological approaches, results in reduced cell proliferation and tumor progression in mouse tumor xenograft models. We developed a PACE4 high-affinity peptide inhibitor, namely, the multi-leucine (ML), and sought to determine whether this peptide could be exploited for the targeting of prostate cancer for diagnostic or molecular imaging purposes. We conjugated a bifunctional chelator 1,4,7-triazacyclononane-1,4,7- triacetic acid (NOTA) to the ML peptide for copper-64 ((64)Cu) labeling and positron emission tomography (PET)- based prostate cancer detection. Enzyme kinetic assays against recombinant PACE4 showed that the NOTA-modified ML peptide displays identical inhibitory properties compared to the unmodified peptide. In vivo biodistribution of the (64)Cu/NOTA-ML peptide evaluated in athymic nude mice bearing xenografts of two human prostate carcinoma cell lines showed a rapid and high uptake in PACE4-expressing LNCaP tumor at an early time point and in PACE4-rich organs. Co-injection of unlabeled peptide confirmed that tumor uptake was target-specific. PACE4-negative tumors displayed no tracer uptake 15 minutes after injection, while the kidneys, demonstrated high uptake due to rapid renal clearance of the peptide. The present study supports the feasibility of using a (64)Cu/NOTA-ML peptide for PACE4-targeted prostate cancer detection and PACE4 status determination by PET imaging but also provides evidence that ML inhibitor-based drugs would readily reach tumor sites under in vivo conditions for pharmacological intervention or targeted radiation therapy., (Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.)

Extrapulmonary manifestations of Mycoplasma pneumoniae are sometimes severe and may even be life-threatening. A 10-year-old patient was hospitalized due to a flu-like illness lasting 48 h with impaired general condition, after an extended stay in Africa. There was an inflammatory syndrome associated with hyponatremia, but malaria was negative. A triple antibiotic therapy with ceftriaxone, amikacin, and josamycin was started. The progression was marked by the appearance of hypoxemia pneumoniae associated with extrarespiratory manifestations. He initially presented with acute polyradiculoneuropathy, followed by thrombotic events associated with polyserositis, polyarthritis, a maculopapular rash, and then a hemophagocytic syndrome. Bacteriological samples isolated M. pneumoniae in nasopharyngeal secretions with a positive serology. The appropriate antibiotic therapy associated with corticosteroids and immunoglobulins led to clinical improvement and the patient progressed toward complete recovery. The pathogenesis of M. pneumoniae infection remains largely unknown. However, two main categories have been proposed. The lung injury is caused by the invasion of the respiratory epithelium, whereas the extrarespiratory manifestations are probably due to immunological disorders. The knowledge of extrarespiratory manifestations and their pathomechanisms allows further adjustments to therapeutic management., (Copyright © 2014. Published by Elsevier SAS.)

Unlabelled: Neonatal thyrotoxicosis is a rare disease. The goal of this study was to analyse main neonatal symptoms, clinical complications and patient's care., Material and Methods: This retrospective study concerned the newborns admitted with neonatal thyrotoxicosis between 1992 and 2004 in the neonatal department of Bordeaux, Toulouse and Pau hospital., Results: Seven of these patients were included in the study. All of the newborns had permanent tachycardia and 3 of them had respiratory failure. Two patients had potentially lethal clinical complications. The first had goitre with tracheal compression. The second developed global heart failure on his 13th day of life. The onset of antithyroid drug treatment was between the 3rd and the 18th day of life. Mean duration of treatment was 50 days. Occurring complications were neutropenia in 3 patients and hypothyroidism in 1 patient. The children were tracked during their first year, and all had normal growth and normal neurological development., Conclusion: The main prognostic factor is the early onset of antithyroid treatment. In our study, 2 patients had potentially lethal clinical complications. Adequate care depends on early spotting of high-risk newborn.

We report the case of an 11-year-old child with delayed development who developed signs of exercise-induced pain in the lower limb muscles after an acute attack of appendicitis. He had difficulty standing up from the sitting position and ascending and descending stairs. The physical examination revealed increased reflex activity in the lower limbs. Initially, blood tests, MRI and EMG were normal. Serum phosphorus and calcium were not assayed. Eight months later, the boy's condition worsened (myopathy gait, hyperlordosis) leading to the possible diagnosis of muscle disease. After muscle biopsy, blood tests revealed hypercalcemia at 3.5 mmol/l (normal 2.2-2.6), hypercalciuria, and hypophosporemia. The diagnosis of primary hyperparathyroidism was confirmed by the abnormal level of parathormone initially (19 ng/ml) and later (156 ng/ml) with hypercalcemia. Medical treatment failed and surgery was performed to remove three and a half parathyroid glands. After removal, blood tests returned to normal in six days and the physical examination in three years. The diagnosis of principal cell hyperplasia was retained at the pathology examination. We found no evidence of hypercalcemia or other endocrinopathy such as multiple endocrine neoplasia (MEN 1 or 2a). Study of the menine gene did not reveal any mutation. Muscle dysfunction suggest possible abnormal phosphocalcium regulation. A normal parathormone level with hypercalcemia reveals inappropriate synthesis and secretion.

Many viruses have been reported to be present in boar semen, particularly during the viremic phase of the diseases. Some of them, such foot-and-mouth disease virus, porcine reproductive and respiratory syndrome virus, swine vesicular disease virus, porcine parvovirus, picornaviruses, adenoviruses, enteroviruses, Japanese encephalitis virus, pseudorabies virus, African swine fever virus and reoviruses are of particular importance and accurate monitoring prior to and during the presence of boars in AI stations is essential. Various methods may be used to detect these viruses in the animals, or even directly in batches of semen. Cell culture, ELISA and PCR are the most accurate and widely used. Because of the high risk of dissemination of disease via AI, the absolute goal is to provide pathogen-free semen and this is feasible with the adequate measures that are discussed briefly in this paper.

Unlabelled: Takayasu arteritis is an uncommon inflammatory arteritis especially in children. We report a case., Case Report: A 11-year-old boy presented dorsalgia with inflammatory syndrome. One year later, the investigation of an hypertension with asymmetric blood pressure revealed an aortic coarctation and a bilateral renal arteries stenosis leading to Takayasu's arteritis diagnosis., Conclusion: Takayasu's arteritis must be evokated in young children in case of associated hypertension and inflammatory syndrome.

Two of every thousand pregnancies are complicated by Graves' disease. Diagnosis is suggested by maternal disorders (tachycardia, exophthalmia, weight loss.) or fetal disorders (tachycardia, intra-uterine growth retardation, preterm birth.). Due to transfer into the fetal compartment of maternal antibodies which stimulate the fetal thyroid by binding to the thyroid thyrotropin (TSH) receptor, only 1% of children born to these mothers are described as having hyperthyroidism. Neonatal thyrotoxicosis disappears with clearance of the maternal antibodies; clinical signs usually disappear during the first four Months of life. The most frequent neonatal clinical signs of thyrotoxicosis are tachycardia, goiter, hyperexcitability, poor weight gain, hepatosplenomegaly, stare and eyelid retraction. Diagnosis is based on determination of the blood level of triiodothyronine (T3), thyroxine (T4) and TSH. To confirm the nature of hyperthyroidism, thyroid-stimulating immunoglobulins (TSI) should be assayed. The kinetics of TSI provides a guide for therapeutic adaptation and disappearance of TSI is a sign of recovery. Rare cases of familial non-autoimmune hyperthyroidism have been shown to be caused by germline mutation of the thyrotropin receptor. We report a case of severe neonatal hyperthyroidism which led to the diagnosis of maternal Graves' disease.