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1

Gouel, Pierrick, Clémence Mahana iti Gatti, Luc de Haro, Alice Liautaud, Jérôme Langrand und Denis Boucaud-Maitre. „Tetrodotoxin Poisoning in Mainland France and French Overseas Territories: A Review of Published and Unpublished Cases“. Toxins 14, Nr. 5 (17.05.2022): 351. http://dx.doi.org/10.3390/toxins14050351.

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Tetrodotoxin is one of the most potent neurotoxins in the aquatic world. This review of published and unpublished reports aims to describe the poisoning cases that have occurred in mainland France and overseas territories. Six articles were included, with 13 poisoning events, individuals or collective (number (n) = 53 patients). Moreover, 13 unpublished poisoning events from toxicovigilance networks were found (n = 17). All cases happened in overseas territories: French Guyana (n = 7), New Caledonia (n = 11), Reunion (n = 35) and French Polynesia (n = 17). The median age was 36 years. The most frequent signs were neurological (81.8%), digestive (54.5%) and general (52.3%). Three cases of dysgueusia and nine cases of urogenital discomfort were observed in French Polynesia. Twelve severe cases were reported, including seven deaths. Only three events (11.5%) were documented by a tetrodotoxin assay. Two families of fish accounted for 91.6% of the poisonings: 33.3% due to the Diodontidae family and 58.3% to the Tetraodontidae family. Although rare, information and collection campaigns on tetrodotoxin poisoning are, therefore, essential.
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2

Doutrelant, Philippe, Nicolas Penel, Charlotte Renaudat, Cassandre Von Platen, Marie Paule Lebitasy, Pauline Smis-Papillon, Bruno Hoen, Eric Lartigau und Yves-Marie Robin. „Very low seroprevalence of sars-cov-2 among health care personnel (HCP) in a French northern comprehensive cancer center at the end of first national containment.“ Journal of Clinical Oncology 39, Nr. 15_suppl (20.05.2021): e13604-e13604. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e13604.

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e13604 Background: To limit SARS-Co-2 transmission in general population, French government had set up a first National containment from March 16, 2020 to June 2, 2020. Furthermore, General Direction of our hospital have implemented and organized physical distancing (telework, teleconsultation, virtual multi-disciplinary board), mask wearing, use of alcoholic ... to limit interpersonal contacts. To assess the impact of this policy, we have carried out a seroprevalence study and identified risk factors for SARS-Co-2 prevalence among HCP in May/June 2020. Methods: This is part of CORSER Study (“Etude séro-épidémiologique du virus SARS-CoV-2 en France d’une Cohorte CORSER-2d de personnels d’établissements de santé »), registered with ClinicalTrials.gov (NCT04325646). Two serological tests were applied in this cohort: S-Flow assay and Luciferase-linked immune-sorbent assay (LuLisa-N test). Results: Between 04 May to 26 June 2020, 392 Osar Lambret Cancer Center employees were included in the present study (about 40% of all staff). The most common jobs were: 92 nurses (23.4%), 80 radiology/radiotherapy manipulators (20.4%), 51 physicians (13.0%), 33 medical interns (8.4%) and 47 administrative staff members (11.9%). There were 98 men (25.0%) and 294 women (75.0%). The mean age was 38.7 (+/- 11.4). There were 7 seropositive cases; the seroprevalence was 1.8% (95%-CI: 0.7-3.6). Among the 7 positive cases, 5 were symptomatic (71.4%). In univariate analysis, factors associated with SARS-Co-2 seroprevalence: symptoms suggesting viral infection within 2 months (OR=5.33), dysgueusia (OR=37.00), anosmia (OR=66.29) and HCP exposed to COVID-19 patient outside work (OR=6.69). Gender, tobacco consumption, O blood group, HCP versus administrative staff, HCP working in different services, HCP providing care to suspected COVID-19 patients, HCP providing high-risk cares were not found to be associated with seropositivity. Of note, we have noticed that BMI≥ 24 kg/m² was associated with seroprevalence (OR=15.45), without biological rational. Conclusions: Our study suggests that strict implementation of protective measures was associated with low SARS-Cov-2 prevalence at the end of first National Containment, including among HCP treating COVID-19+ patients. HCPs seroprevalence seemed lower than seroprevalence of the general population at the same period (4-5%). Clinical trial information: NCT04325646.
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3

Fleming, Mark T., Dana E. Rathkopf, Jackie Gibbons, Amy C. Peterson, Alison Hannah, David Forer, Howard I. Scher und Michael J. Morris. „Results from a phase I study of enzalutamide in combination with docetaxel in men with prostate cancer.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 5066. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.5066.

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5066 Background: Enzalutamide (ENZA) is a novel androgen receptor (AR) inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (DOC). DOC also prolongs survival in mCRPC and also appears to have anti-tumor effects mediated through the androgen-receptor axis, providing a compelling rationale for combining the two agents. CYP3A4 plays a role in DOC clearance and is induced by ENZA. We therefore conducted a phase I study to explore the PK and safety profiles of this combination. Methods: This study (NCT01565928) evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: Twenty-two pts were enrolled, 4 did not receive 2 full doses of DOC. As of 21 Sept 2012, preliminary PK and C1 and C2 safety data were available from 15 pts. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000/mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone.Final PK and updated tolerability and efficacy data beyond Cycle 2 will be presented. Conclusions: In mCRPC pts, ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.
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4

Fleming, Mark T., Dana E. Rathkopf, Jackie Gibbons, Amy C. Peterson, Alison Hannah, David Forer, Howard I. Scher und Michael J. Morris. „Enzalutamide in combination with docetaxel in men with prostate cancer (PC): Preliminary results from a phase I study.“ Journal of Clinical Oncology 31, Nr. 6_suppl (20.02.2013): 63. http://dx.doi.org/10.1200/jco.2013.31.6_suppl.63.

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63 Background: Enzalutamide (ENZA), a novel oral androgen receptor (AR) inhibitor, inhibits AR signaling via inhibition of androgen binding to the AR, AR nuclear translocation, and nuclear AR-DNA binding. ENZA demonstrated a survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (Scher et al, NEJM 2012; 367:1187). A Phase III study in men with progressive chemotherapy-naïve disease (PREVAIL), is ongoing. Docetaxel (DOC) is the current standard first-line chemotherapy for mCRPC. CYP3A4, which plays a role in DOC clearance, is induced by ENZA. Patients (pts) eligible to receive DOC may benefit from continued AR inhibition with ENZA, provided the combination is well tolerated with no unacceptable drug-drug interactions. Methods: This study evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks, with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: As of 21 Sept. 2012, 22 pts have been enrolled, 3 did not complete both C1 and C2; PK and C1 and C2 safety data are currently available from 15 pts reported here. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone. Conclusions: This is the first evaluation of ENZA given in combination with DOC.In mCRPC pts ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.
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5

Boulinguez, S., M. Mularcyk und R. Viraben. „Dysgueusie amère aux pignons de pin“. Annales de Dermatologie et de Vénéréologie 141, Nr. 3 (März 2014): 220–22. http://dx.doi.org/10.1016/j.annder.2014.01.006.

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6

Aynaou, H., F. M. O. Elilie und H. Latrech. „Hyperparathyroïdie primaire et dysgueusie : une association inhabituelle“. Annales d'Endocrinologie 77, Nr. 4 (September 2016): 442–43. http://dx.doi.org/10.1016/j.ando.2016.07.556.

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7

Roblot, P., M. Paccalin, F. Roy-Péaud, C. Landron, L. Juhel und B. Becq-Giraudon. „Les dysgueusies acquises : après la iatrogénie…“. La Revue de Médecine Interne 22 (Juni 2001): 72–73. http://dx.doi.org/10.1016/s0248-8663(01)83426-3.

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8

Ruhin-Poncet, B., A. Guerre, P. Goudot und C. Escande. „Dysosmies et dysgueusies post-traumatiques : aspects médicolégaux“. Revue de Stomatologie et de Chirurgie Maxillo-faciale 111, Nr. 5-6 (November 2010): 296–98. http://dx.doi.org/10.1016/j.stomax.2010.10.009.

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9

Gutiérrez-Cid, Isabel, Arthur Lionnet und Yann Péréon. „Dysphonie et dysgueusie aiguës : l’ENMG reste un élément clé du diagnostic“. Neurophysiologie Clinique/Clinical Neurophysiology 46, Nr. 3 (Juni 2016): 225. http://dx.doi.org/10.1016/j.neucli.2016.06.020.

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10

Cabon, M., G. Cinquetti, C. Cuvelier, X. Roux, C. Villa, J. Bordachar, D. Maugard et al. „Une carence de mauvais goût : à propos d’une dysgueusie révélatrice d’une carence martiale“. La Revue de Médecine Interne 33 (Juni 2012): S96—S97. http://dx.doi.org/10.1016/j.revmed.2012.03.128.

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11

Le Moigne, M., M. Saint-Jean, A. Jirka, G. Quéreux, L. Peuvrel, A. Brocard, A. Khammari, D. Darmaun und B. Dréno. „Dysgueusie et perte de poids sous vismodegib : intérêt d’une prise en charge nutritionnelle spécifique“. Annales de Dermatologie et de Vénéréologie 140, Nr. 12 (Dezember 2013): S392. http://dx.doi.org/10.1016/j.annder.2013.09.069.

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12

Crameri, Manuel, Renzo Bassetti, Peter Werder und Johannes Kuttenberger. „Tonsillolithes sur l’orthopantomogramme (OPT)“. SWISS DENTAL JOURNAL SSO – Science and Clinical Topics 126, Nr. 1 (11.01.2016): 33–36. http://dx.doi.org/10.61872/sdj-2016-01-04.

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La lithiase amygdalienne est caractérisée par la présence de concrétions calciques (tonsillolithes) dans les cryptes des amygdales. Le plus souvent, ces concrétions se situent dans les amygdales palatines. Leur prévalence est de 16 à 46,1%. Les tonsillolithes peuvent provoquer une mauvaise haleine chronique (halitose), une toux irritative, une dysphagie, des otalgies, des sensations de corps étranger, un mauvais goût dans la bouche (dysgueusie) ainsi que des épisodes récurrents d’amygdalite et des ulcérations de l’amygdale. Mais ces concrétions sont souvent asymptomatiques. En général, les calculs amygdaliens sont découverts fortuitement lors de l’évaluation d’un orthopantomogramme (OPT), même s’ils ne sont pas toujours reconnus comme tels. Le présent travail rapporte deux cas de lithiase amygdalienne asymptomatique. Les tonsillolithes avaient été repérés à l’OPT dans la région de la branche montante de la mandibule, et leur présence a été confirmée par la suite au scanner (CT) et respectivement à l’IRM.
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Thieblemont, Catherine, Anastasios Stathis, Giorgio Inghirami, Lionel Karlin, Franck Morschhauser, Mary Gleeson, Florence Broussais et al. „A Phase 1 Study of the BET-Bromodomain Inhibitor OTX015 in Patients with Non-Leukemic Hematologic Malignancies“. Blood 124, Nr. 21 (06.12.2014): 4417. http://dx.doi.org/10.1182/blood.v124.21.4417.4417.

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Abstract Rationale: BET-bromodomain (BRD) proteins are DNA readers that bind acetylated histone (H) tails preferentially at hyperacetylated superenhancer promoter regions and trigger gene transcription. The expression of several oncogenes, including c-MYC, is epigenetically regulated by BRD. OTX015 is a BRD 2, 3 and 4 inhibitor that prevents BRD binding to acetylated H4 and downregulates gene expression of BRD-dependent genes. OTX015 has been shown to inhibit the growth of diffuse large B-cell lymphoma (DLBCL) cells in vitroand in animal models. Patients & Methods: Patients with non-leukemic hematologic malignancies refractory or resistant to standard therapies were enrolled in an ongoing phase 1 clinical study. Lymphoma patients had to have failed at least two lines of systemic therapy and have evaluable disease. OTX015 was given orally daily (QD) without a planned rest period, with 3-week cycles (cy). Successive cohorts of 3-6 patients were treated at increasing dose levels (DL) from 10 to 120 mg QD to determine the maximum tolerated dose (MTD) or the biologically optimal dose. A BID schedule was tested at DL 4 (40 mg x 2). Pharmacokinetics was assessed on day 1 and residual concentrations were measured on days 2, 8 and 15. Lymphoma assessment was performed according to Cheson’s criteria every 6-8 weeks. Results: From January 2013 to June 2014, 37 non-leukemic patients (18 DLBCL, 9 other lymphomas, 10 myeloma) were treated over 5 dose levels, 33 of whom were evaluable for dose limiting toxicity (DLT). Median age was 67 years (range 27-83), 22 patients were male, 27 patients had ECOG 0-1. Patients had a median of 4 prior therapy lines (range 2-8), including 10 patients with autologous stem cell transplantation. The median number of OTX015 cycles administered was 2 (range 1-10+). No DLTs were observed through DL4 (80 mg QD). Asymptomatic and rapidly reversible grade 4 thrombocytopenia was the DLT at DL4 BID (40 mg x2) and 120 mg QD continuous. Sixteen patients experienced grade 3-4 thrombocytopenia and 3 patients had asymptomatic grade 3-4 neutropenia. Grade 3 non-hematologic toxicities were diarrhea, vomiting, hyperglycemia, and hypernatremia (1 patient each). Other toxicities were non-cumulative grade 1-2 gastrointestinal events (8 patients with diarrhea, 3 dysgueusia, 2 vomiting, 1 nausea, 1 anorexia, 1 abdominal pain), hyperglycemia (7 patients), skin rash (3 patients), asymptomatic coagulation factor VII decrease (2 patients), and direct bilirubin increase (1 patient). Dose proportional plasma concentrations were observed and trough concentrations > 500 nM occurred regularly from 80 mg/day. Additional patients are currently being treated at 80 mg QD or with various discontinuous schedules at 120 mg (5 days on/2 days off, 2 weeks on/1 week off, 1 week on/2 weeks off) to determine the recommended regimen. Clinically relevant activity was reported in 6 patients treated from 40 to 120 mg, including one CR (120 mg, 17+ weeks [wks]) and 1 PR (80 mg, 28 wks), both in DLBCL patients failing 3-4 prior therapy lines, and both with clinical benefit. Four other patients (two with DLBCL, one follicular, and one lymphoplasmacytic lymphoma) had minor tumor shrinkage with clinical benefit (40 mg, 36+ wks; 80 mg, 14 wks; 120 mg 15 wks; 120 mg, 17 wks). Conclusions: OTX015 single agent exhibits clinically significant activity against resistant DLBCL with two responses and two minor tumor shrinkages among nine evaluable patients treated at doses ≥ 80 mg. Centralized pathology review including immunohistochemistry profiling is being performed retrospectively, and will be prospective in a DLBCL expansion cohort. Updated data including recommended regimen and correlations between clinical activity and biomarkers will be presented. Disclosures Thieblemont: Oncoethix SA: Research Funding. Stathis:Oncoethix SA: Research Funding. Inghirami:Oncoethix SA: Research Funding. Karlin:Oncoethix SA: Research Funding. Morschhauser:Oncoethix SA: Research Funding. Gleeson:Oncoethix SA: Research Funding. Broussais:Oncoethix SA: Research Funding. Amorim:Oncoethix SA: Research Funding. Salles:Oncoethix SA: Research Funding. Facon:Oncoethix SA: Research Funding. Cunningham:Oncoethix SA: Research Funding. Vey:Oncoethix SA: Research Funding. Bourdel:Oncoethix SA: Employee of study CRO Other. Herait:Oncoethix SA: CMO and Shareholder Other. Zucca:Oncoethix SA: Research Funding.
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14

Carignan, Alex, Louis Valiquette, Cynthia Grenier, Jean Berchmans Musonera, Delphin Nkengurutse, Anaïs Marcil-Héguy, Kim Vettese et al. „Anosmie et dysgueusie associées à l’infection au SRAS-CoV-2: étude cas–témoins appariée selon l’âge“. Canadian Medical Association Journal 192, Nr. 46 (15.11.2020): E1487—E1492. http://dx.doi.org/10.1503/cmaj.200869-f.

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15

Jirka, A., M. Saint-Jean, M. Le Moigne, G. Quéreux, L. Peuvrel, A. Brocard, A. Khammari, D. Darmaun und B. Dréno. „P273: Dysgueusie et dénutrition au cours des traitements par le vismodegib : effet d’une prise en charge nutritionnelle“. Nutrition Clinique et Métabolisme 28 (Dezember 2014): S212. http://dx.doi.org/10.1016/s0985-0562(14)70915-x.

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16

Dombret, Hervé, Claude Preudhomme, Céline Berthon, Emmanuel Raffoux, Xavier Thomas, Norbert Vey, Carlos Gomez-Roca et al. „A Phase 1 Study of the BET-Bromodomain Inhibitor OTX015 in Patients with Advanced Acute Leukemia“. Blood 124, Nr. 21 (06.12.2014): 117. http://dx.doi.org/10.1182/blood.v124.21.117.117.

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Abstract Rationale: BET-bromodomain (BRD) proteins play a major role in the epigenetic regulation of gene transcription, notably of genes with superenhancer promoter regions including many oncogenes, such as MYC. OTX015 is a specific BRD 2, 3 and 4 inhibitor that blocks oncogene transcription, and triggers growth inhibition and apoptosis in acute leukemia cell lines and patient cells in vitro (Braun et al. ASH Annual Meeting 2013). Based on these findings, a Phase 1 study of OTX015 was designed for patients with advanced acute leukemia. Patients & Methods: Patients with various unselected relapsed/refractory leukemia subtypes for which no standard therapy options were available were enrolled in this ongoing Phase 1 study. Patients aged < 60 years had to have failed at least two lines of therapy and those aged >60 years at least one line. At least 5% bone marrow leukemic blasts were required at study entry. OTX015 was given orally, daily for 14 days of 21-day cycles (cy). The dose was escalated from 10 to 160 mg daily (QD) according to a standard 3+3 dose-escalation design, to determine the maximum tolerated dose (MTD) or biologically optimal dose. A BID schedule was tested at dose level (DL) 4 (40 mg x 2) and a continuous schedule at 120 mg. Pharmacokinetics was studied on day 1 and residual concentrations were measured on days 2, 8 and 15. Responses were assessed on blood and bone marrow aspirations at baseline, days 8, 22 and 43. Blasts at baseline and day 8 were stored for pharmacodynamic biomarker evaluation. Cytogenetic and molecular markers were collected based on center practice. Results: From January 2013 to June 2014, 36 patients were treated over 6 dose levels: 33 with acute myeloid leukemia (AML), 2 with acute lymphoblastic leukemia and 1 with refractory anemia with excess blasts. Median age was 70 years (range 19-85), 20 patients were male, 29 patients had ECOG 0-1, and 16 AML patients had normal karyotype. Patients had a median of 2 prior therapy lines (range 1-4). The median number of OTX015 cycles administered was 2 (range 1-14+), including 9 patients with >3 cycles. Among the 28 patients evaluable for dose limiting toxicity (DLT), no DLTs were observed through DL5 (120 mg QD). The MTD was exceeded at DL6 (160 mg QD) with one patient experiencing grade 3 diarrhea and another grade 3 fatigue and anorexia. The main toxicities were non-cumulative grade 1-2 gastrointestinal events (6 patients diarrhea, 3 dysgueusia, 3 abdominal pain, 3 nausea, 1 anorexia), hyperglycemia (3 patients), coagulation factor VII decrease (6 patients) and direct bilirubin increase (3 patients) (two latter AEs asymptomatic). These toxicities were mainly observed at QD doses above 80 mg and with 40 mg BID. Dose proportional plasma concentrations were observed and trough concentrations > 500 nM (in vitro active concentrations) were regularly observed from 80 mg/day. Clinically relevant activity was reported in 5 AML patients treated at 10, 40 and 80 mg, including one sustained CR from cy 4 to cy 12 (40 mg QD) and one CR with incomplete platelet recovery (CRp) from cy 2 to cy 5 (80 mg QD). Two patients (10 mg QD, 40 mg QD) had partial blast clearance (disappearance of peripheral blasts and decrease >50% in bone marrow blast percentage) and the remaining patient (40 mg BID) had gum hypertrophy resolution. Four of these 5 patients had secondary or therapy-related AML, 4 had normal karyotype and 2 had an NPM1 gene mutation. Conclusions: OTX015 single agent exhibits antileukemic activity over a wide range of DLs and plasma concentrations in patients with advanced AML. MTD is exceeded at 160 mg QD. The safe recommended dose and schedule is close to being identified. Central extensive molecular marker analysis is being performed and will be prospectively implemented in an expansion cohort. Updated data will be presented and will include correlations between regimen, pharmacokinetics, clinical activity and molecular profile. Table Dose (Schedule) N pts evaluable Evidence of activity DLT 10 QD (14/21) 3 1 20 QD (14/21) 3 40 QD(14/21) 4 1 (CR) 80 QD(14/21) 3 2 (1 CRp) 40 BID (14/21) 6 1 120 QD (14/21) 3 120 QD (21/21) 3 160 QD (14/21) 3 Diarrhea (1) Anorexia/fatigue (1) Disclosures Dombret: Oncoethix SA: Research Funding. Preudhomme:Oncoethix SA: Research Funding. Berthon:Oncoethix SA: Research Funding. Raffoux:Oncoethix SA: Research Funding. Thomas:Oncoethix SA: Research Funding. Vey:Oncoethix SA: Research Funding. Gomez-Roca:Oncoethix SA: Research Funding. Ethell:Oncoethix SA: Research Funding. Yee:Oncoethix SA: Research Funding. Bourdel:Oncoethix SA: Employee of study CRO Other. Herait:Oncoethix SA: CMO and Shareholder Other. Michallet:Oncoethix SA: Research Funding. Recher:Oncoethix SA: Research Funding. Roumier:Oncoethix SA: Research Funding. Quesnel:Oncoethix SA: Research Funding.
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Bernardor, Julie, Sacha Flammier, Sara Cabet, Sandrine Lemoine, Roland Chapurlat, Arnaud Molin, Aurélia Bertholet-Thomas und Justine Bacchetta. „Intermittent Bi-Daily Sub-cutaneous Teriparatide Administration in Children With Hypoparathyroidism: A Single-Center Experience“. Frontiers in Pediatrics 9 (08.11.2021). http://dx.doi.org/10.3389/fped.2021.764040.

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Introduction: The use of teriparatide has been reported in children with hypoparathyroidism as an investigational physiologic replacement therapy.Methods: We aimed to retrospectively report our pediatric experience of bi-daily sub-cutaneous teriparatide. Results are presented as median (25th−75th quartile). As part of the routine follow-up of these patients with hypoparathyroidism, total calcium at H0 (i.e., just before injection) and H4 (i.e., 4 h after teriparatide injection) and other biomarker parameters were regularly assessed.Results: At a median age of 10.7 (8.1–12.6) years, an estimated glomerular filtration rate (eGFR) of 110 (95–118) mL/min/1.73 m2, calcium levels of 1.87 (1.81–1.96) mmol/L and an age-standardized phosphate of 3.8 (2.5–4.9) SDS, teriparatide therapy was introduced in 10 patients at the dose of 1.1 (0.7–1.5) μg/kg/day (20 μg twice daily), with further adjustment depending on calcium levels. Six patients already displayed nephrocalcinosis. Severe side effects were reported in one child: two episodes of symptomatic hypocalcemia and one of iatrogenic hypercalcemia; one teenager displayed dysgueusia. Calcium levels at H0 did not significantly increase whilst calcium at H4 and phosphate levels significantly increased and decreased, respectively. After 12 months, eGFR, calcium and age-standardized phosphate levels were 108 (90–122) mL/min/1.73 m2, 2.36 (2.23–2.48) mmol/L, 0.5 (−0.1 to 1.5), and 68 (63–74) nmol/L, respectively, with a significant decrease in phosphate levels (p = 0.01). Urinary calcium and calcium/creatinine ratio remained stable; no nephrolithiasis was observed but two moderate nephrocalcinosis appeared.Conclusion: Intermittent teriparatide therapy significantly improves calcium and phosphate control, without increasing calciuria. It appears to be safe and well-tolerated in children.
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