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1. Development of a Quinoa-Based Fermentation Medium for Propagation of Lactobacillus Plantarum and Weissella Confusa in Opaque Beer Production

Author

Shepherd Manhokwe, Tatenda Musarurwa, Talknice Z. Jombo, Desmond T. Mugadza, Amiel Mugari, Joseph Bare, Scelo Mguni, Fidelis Chigondo, and Jane Tafadzwa Muchekeza

Subjects
Microbiology, QR1-502
Abstract

Product inconsistency of opaque beer has for long been a tenacious problem in the brewing industry since the current process relies on spontaneous lactic acid fermentation. In order to impede this challenge, there is a need to add lactic acid bacteria (LAB) starter cultures in opaque beer brewing to improve its organoleptic qualities. This study sought to develop a quinoa-based fermentation medium for propagation of Lactobacillus plantarum and Weissella confusa as potential starter cultures in opaque beer production. An evaluation of the stability and tolerance of the LAB under various stress conditions was also done. Fermentation wort from opaque beer brewing and different quinoa-based synthetic media with varying nutritional components was prepared for propagation of LAB. Physiochemical analyses which included pH, Brix value and total titratable acidity (TTA) of monocultured and cocultured synthetic media were measured. The measurements were done at 24 h time intervals ranging from 0 to 96 h. Tolerance studies which included the effect of heat shock, cold shock, oxidative stress and osmotic pressure on the survival rate of LAB were conducted to determine the stability of LAB. MRS with L. plantarum monoculture (MRSp) had a notable change in pH from 4.5 to 3.6 after 24 h. The cocultured (M5p + w) synthetic media and cocultured MRS (MRSp + w) also exhibited change in pH from 4.3 to 3.2 and 4.3 to 3.3, respectively, after 72 h. Brix value in all media samples decreased after 24 h except for the uninoculated MRS sample (MRS C). The synthetic and coculture medium (M5p + w) exhibited an increase in TTA (0.79% (m/v) lactic acid) within the first 24 h. Exposure to heat shock had a significance effect (p

Published
2025
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2. Physiologically‐based pharmacokinetic modeling of the drug–drug interaction between ivacaftor and lefamulin in cystic fibrosis patients

Author

Magali Amiel, Alice Ke, Steven P. Gelone, Hannah M. Jones, and Wolfgang Wicha

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Abstract Lefamulin is being evaluated as a treatment for bacterial exacerbations in cystic fibrosis (CF). Ivacaftor is approved for the treatment of patients with CF. Lefamulin is a moderate CYP3A inhibitor and co‐administration with ivacaftor may result in a drug–drug interaction (DDI). A CF population was built based on literature using the Simcyp Simulator. A previously developed and validated physiologically‐based pharmacokinetic (PBPK) model for ivacaftor was used. A PBPK model for lefamulin was developed and verified. Predicted concentrations and pharmacokinetic (PK) parameters for both ivacaftor and lefamulin in healthy subjects and patients with CF were in reasonable agreement with observed data (within 1.4‐fold, majority within 1.25‐fold). The lefamulin model as a CYP3A4 perpetrator was validated using a different Ki value for oral (p.o.) and intravenous (i.v.) routes. The simulated changes in area under the curve of ivacaftor in patients with CF when co‐administered with p.o. and i.v. lefamulin were weak‐to‐moderate. The predicted change in ivacaftor PK when co‐administered with oral lefamulin was less than observed between ivacaftor and fluconazole. These results suggest a low liability for a DDI between lefamulin and ivacaftor in patients with CF.

Published
2024
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4. A retrospective study on the prognostic factors and success, survival, and failure outcomes of treated endodontic‐periodontal lesions

Author

Ingar Wong, An Ton, Amiel J. Cassidy, Nicolette Fozzard, Lavanya Ajay Sharma, Robert M. Love, and Ajay Sharma

Subjects
endodontic‐periodontal lesion, endodontics, periodontitis, prognostic factor, Dentistry, RK1-715
Abstract

Abstract Objectives The objective of this retrospective study was to determine possible prognostic factors of endodontic‐periodontal lesions and to compare success, survival, and failure outcomes of treated endodontic‐periodontal lesions across different treatment modalities, demographic variables, and anatomical tooth variations. Materials and Methods Data was collected from patient records in the patient management system (Salud, Titanium Solutions) from the Griffith University Dental Clinic between January 2008 and December 2021. The search strategy used the terms “endodontic periodontal lesion,” “periodontal endodontic lesion,” “endo perio lesion,” “perio endo lesion,” and “EPL.” The 88 cases which met inclusion and exclusion criteria were analyzed. Results The overall success rate was 46.6%, with 21.6% of teeth surviving and 31.8% of teeth failing. Bone loss extending to the apical third (OR = 0.3, 95% CI [0.104, 0.866]), and probing depths of 5–7 mm (OR = 0.147, 95% CI [0.034, 0.633]) and 8‐10 mm (OR = 0.126, 95% CI [0.029, 0.542]) were associated with a statistically significant lower odds of success (p

Published
2024
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5. Is serum‐derived exosomal hTERT transcript a marker of oncogenic activity in primary brain tumors? An exploratory study

Author

Orit Uziel, Andrew A. Kanner, Einat Beery, Sapir Lev, Meir Lahav, Suzana Horn‐Fichman, Sagi Har Nof, Yuseph Laviv, S. Yust‐Katz, Alexandra Amiel, Ramez Abu Shkara, Mustafa Siddeeq, Adva Levy‐Barda, Pia Raanani, Yaron Sela, Zvi Cohen, and Tali Siegal

Subjects
atypical meningioma, exosomes, glioblastoma, liquid biopsy, meningioma, telomerase, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables telomere maintenance and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity. This study explored whether a liquid biopsy that analyses blood derived exosomal hTERT transcript (e‐hTERT‐trans) may serve as such a biomarker in gliomas and meningiomas when compared to healthy controls. Methods Exosomes were isolated from the pre‐operative sera of patients' samples stored in the biobank of both Rabin and Sheba Medical Centers. The levels of e‐hTERT‐trans were measured in 81 healthy controls, 117 meningiomas, 17 low‐grade gliomas, and 61 glioblastomas. Clinical parameters of the patients were collected retrospectively and compared to the levels of the e‐hTERT‐trans. Results The upper normal limit of controls e‐hTERT‐trans was 1.85 relative quantitation (RQ). The rate of detection increased with rising tumor grade and correlated with tumor recurrence in meningiomas: mean RQ without recurrence (2.17 ± 11.7) versus with recurrence (3.59 ± 4.42; p = 0.002). In glioblastomas, preoperative measurements correlated with tumor volume and with the disease course on serial sampling. Conclusions We demonstrated for the first time that the expression of e‐hTERT‐trans transcript can be measured in the serum of primary brain tumors. This exosomal marker carries the potential to serve as a biomarker once used in conjunction with other clinical and radiological parameters. Future studies are required to investigate whether the sensitivity could be augmented and whether it can be implemented into routine patients care.

Published
2024
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6. Cross‐cultural adaptation of the Hebrew Nasal Obstruction Symptom Evaluation (NOSE) scale

Author

Amani Daoud, Netanel Eisenbach, Ohad Ronen, Amiel Dror, Tali Jane Ohayon, Majd Hajouj, Eyal Sela, and Tal Marshak

Subjects
nasal obstruction, NOSE scale, PROMS, quality of life, validation study, Otorhinolaryngology, RF1-547, Surgery, RD1-811
Abstract

Abstract Objective Nasal obstruction is a common complaint. The Nasal Obstruction Symptom Evaluation scale (NOSE) is a reliable validated tool used to assess the quality of life of patients with nasal obstruction. The purpose of this study is to validate the Hebrew version of the NOSE scale (He‐NOSE). Methods A prospective instrument validation was conducted. The NOSE scale was translated primarily from English to Hebrew and then back from Hebrew to English according to the accepted guidelines of the cross‐cultural adaptation process. The study group included surgery candidates suffering from nasal obstruction due to a deviated nasal septum and/or inferior turbinate hypertrophy. The study group completed the validated He‐NOSE questionnaire twice prior to the surgery and once again, a month post‐surgery. A control group of individuals with no history of nasal complaints or surgeries was asked to complete the questionnaire once. Reliability, internal consistency, validity, and responsiveness to change of the He‐NOSE were evaluated. Results Fifty‐three patients and 100 controls were included in this study. The scale showed excellent ability to discriminate between the study and the control group, exhibiting significantly lower scores in the control group (73.8 and 7 average scores respectively, p

Published
2023
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7. Predictors of PrEP awareness, PrEP discussion and interest in long‐acting injectable PrEP among Filipina transfeminine adults

Author

Arjee Javellana Restar, Ma Irene Quilantang, Jeffrey Wickersham, Alex Adia, John Guigayoma, Amiel Nazer Bermudez, Omar Galárraga, Dalmacio Dennis Flores, Susan Cu‐Uvin, Jennifer Nazareno, Don Operario, and Olivia Sison

Subjects
HIV, PrEP, transfeminine, transgender, Philippines, implementation, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Introduction Transfeminine adults are impacted by the HIV epidemic in the Philippines, and newly approved modalities of pre‐exposure prophylaxis (PrEP), including long‐acting injectable (LAI‐PrEP), could be beneficial for this group. To inform implementation, we analysed PrEP awareness, discussion and interest in taking LAI‐PrEP among Filipina transfeminine adults. Methods We utilized secondary data from the #ParaSaAtin survey that sampled Filipina transfeminine adults (n = 139) and conducted a series of multivariable logistic regressions with lasso selection to explore factors independently associated with PrEP outcomes, including awareness, discussion with trans friends and interest in LAI‐PrEP. Results Overall, 53% of Filipina transfeminine respondents were aware of PrEP, 39% had discussed PrEP with their trans friends and 73% were interested in LAI‐PrEP. PrEP awareness was associated with being non‐Catholic (p = 0.017), having previously been HIV tested (p = 0.023), discussing HIV services with a provider (p

Published
2023
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8. Columbia COVID‐19 Student Service Corps: Harnessing student skills and galvanizing the power of service learning

Author

Stephanie A. Grilo, Marina Catallozzi, Urmi Desai, Aubrie Swan Sein, Cibel Quinteros Baumgart, George Timmins, David Edelman, and Jonathan M. Amiel

Subjects
COVID‐19, medical education, service learning, Biology (General), QH301-705.5
Abstract

Abstract The COVID‐19 pandemic in New York City led to the forced rapid transformation of the medical school curriculum as well as increased critical needs to the health system. In response, a group of faculty and student leaders at CUIMC developed the COVID‐19 Student Service Corps (Columbia CSSC). The CSSC is an interprofessional service‐learning organization that galvanizes the skills and expertise of faculty and students from over 12 schools and programs in the response to the COVID‐19 pandemic, and is agile enough to shift and respond to future public health and medical emergencies. Since March 2020, over 30 projects have been developed and implemented supporting needs identified by the health system, providers, faculty, staff, and students as well as the larger community. The development of the CSSC also provided critical virtual educational opportunities in the form of service learning for students who were unable to have any in‐person instruction. The CSSC model has been shared nationally and nine additional chapters have started at academic institutions across the country.

Published
2021
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11. Real-life effectiveness of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir

Author

Universidad de Sevilla. Departamento de Biología Celular, Ruiz Cobo, Juan Carlos, Llaneras, Jordi, Forns, Xavier, Gallego Moya, Adolfo, Conde Amiel, Isabel, Arencibia, Ana, Rodríguez Seguel, Elisa del Pilar, Buti, María, Universidad de Sevilla. Departamento de Biología Celular, Ruiz Cobo, Juan Carlos, Llaneras, Jordi, Forns, Xavier, Gallego Moya, Adolfo, Conde Amiel, Isabel, Arencibia, Ana, Rodríguez Seguel, Elisa del Pilar, and Buti, María

Abstract

Background Sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is the recommended rescue therapy for patients with chronic hepatitis C infection who fail direct-acting antivirals (DAAs). Data are limited on the effectiveness of this treatment after the current first-line therapies. Our aim was to analyse the effectiveness and safety of SOF/VEL/VOX among patients failing sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB). Methods Retrospective multicentre study (26 Spanish hospitals), including chronic hepatitis C patients unsuccessfully treated with SOF/VEL or GLE/PIB, and retreated with SOF/VEL/VOX ± ribavirin for 12 weeks between December 2017 and December 2022. Results In total, 142 patients included: 100 (70.4%) had failed SOF/VEL and 42 (29.6%) GLE/PIB. Patients were mainly men (84.5%), White (93.9%), with hepatitis C virus genotype (GT) 3 (49.6%) and 47.2% had liver cirrhosis. Sustained virological response (SVR) was evaluated in 132 patients who completed SOF/VEL/VOX and were followed 12 weeks after end of treatment; 117 (88.6%) achieved SVR. There were no significant differences in SVR rates according to initial DAA treatment (SOF/VEL 87.9% vs. GLE/PIB 90.2%, p = 0.8), cirrhosis (no cirrhosis 90% vs. cirrhosis 87.1%, p = 0.6) or GT3 infection (non-GT3 91.9% vs. GT3 85.5%, p = 0.3). However, when considering the concurrent presence of SOF/VEL treatment, cirrhosis and GT3 infection, SVR rates dropped to 82.8%. Ribavirin was added in 8 (6%) patients, all achieved SVR. Conclusion SOF/VEL/VOX is an effective rescue therapy for failures to SOF/VEL or GLE/PIB, with an SVR of 88.6%. Factors previously linked to lower SVR rates, such as GT3 infection, cirrhosis and first-line therapy with SOF/VEL were not associated with lower SVRs.

Published
2024

12. 3q29 duplications: A cohort of 46 patients and a literature review

Author

Massier, Marie, primary, Doco‐Fenzy, Martine, additional, Egloff, Matthieu, additional, Le Guillou, Xavier, additional, Le Guyader, Gwenaël, additional, Redon, Sylvia, additional, Benech, Caroline, additional, Le Millier, Karine, additional, Uguen, Kevin, additional, Ropars, Juliette, additional, Sacaze, Elise, additional, Audebert‐Bellanger, Séverine, additional, Apetrei, Andreea, additional, Molin, Arnaud, additional, Gruchy, Nicolas, additional, Vincent‐Devulder, Aline, additional, Spodenkiewicz, Marta, additional, Jacquin, Clémence, additional, Loron, Gauthier, additional, Thibaud, Marie, additional, Delplancq, Geoffroy, additional, Brisset, Sophie, additional, Lesieur‐Sebellin, Marion, additional, Malan, Valérie, additional, Romana, Serge, additional, Rio, Marlène, additional, Marlin, Sandrine, additional, Amiel, Jeanne, additional, Marquet, Valentine, additional, Dauriat, Benjamin, additional, Moradkhani, Kamran, additional, Mercier, Sandra, additional, Isidor, Bertrand, additional, Arpin, Stéphanie, additional, Pujalte, Mathilde, additional, Jedraszak, Guillaume, additional, Pebrel‐Richard, Céline, additional, Salaun, Gaëlle, additional, Laffargue, Fanny, additional, Boudjarane, John, additional, Missirian, Chantal, additional, Chelloug, Nora, additional, Toutain, Annick, additional, Chiesa, Jean, additional, Keren, Boris, additional, Mignot, Cyril, additional, Gouy, Evan, additional, Jaillard, Sylvie, additional, Landais, Emilie, additional, and Poirsier, Céline, additional

Published
2024
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15. Fine‐scale substrate heterogeneity in green roof plant communities: The constraint of size

Author

Amiel Vasl, Bracha Y. Schindler, Gyongyver J. Kadas, and Leon Blaustein

Subjects
neutral theory, niche theory, plant community assemblage, plant–soil interactions, Ecology, QH540-549.5
Abstract

Abstract Heterogeneity–diversity relationship (HDR) is commonly shown to be positive in accordance with classic niche processes. However, recent soil‐based studies have often found neutral and even negative HDRs. Some of the suggested reasons for this discrepancy include the lack of resemblance between manipulated substrate and natural settings, the treated areas not being large enough to contain species' root span, and finally limited‐sized plots may not sustain focal species’ populations over time. Vegetated green roofs are a growing phenomenon in many cities that could be an ideal testing ground for this problem. Recent studies have focused on the ability of these roofs to sustain stable and diverse plant communities and substrate heterogeneity that would increase niches on the roof has been proposed as a method to attain this goal. We constructed an experimental design using green roof experimental modules (4 m2) where we manipulated mineral and organic substrate component heterogeneity in different subplots (0.25 m2) within the experimental module while maintaining the total sum of mineral and organic components. A local annual plant community was seeded in the modules and monitored over three growing seasons. We found that plant diversity and biomass were not affected by experimentally created substrate heterogeneity. In addition, we found that different treatments, as well as specific subplot substrates, had an effect on plant community assemblages during the first year but not during the second and third years. Substrate heterogeneity levels were mostly unchanged over time. The inability to retain plant community composition over the years despite the maintenance of substrate differences supports the hypothesis that maintenance of diversity is constrained at these spatial scales by unfavorable dispersal and increased stochastic events as opposed to predictions of classic niche processes.

Published
2019
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16. Peripheral blood telomere alterations in ground glass opacity (GGO) lesions may suggest malignancy

Author

Matthew Koslow, David Shitrit, Lilach Israeli‐Shani, Orit Uziel, Einat Beery, Alexandra Osadchy, Yael Refaely, Gali Epstein Shochet, and Aliza Amiel

Subjects
Adenocarcinoma, blood marker, GGO, senescence, telomere, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

A ground glass opacity (GGO) lung lesion may represent early stage adenocarcinoma, which has an excellent prognosis upon prompt surgical resection. However, GGO lesions have broad differential diagnoses, including both benign and malignant lesions. Our objective was to study telomere length and telomerase activity in patients with suspected lung cancer in which GGO was the predominant radiographic feature. Knowledge of telomere biology may help distinguish malignant from benign radiographic lesions and guide risk assessment of these lesions. Peripheral blood samples were taken from 22 patients with suspected adenocarcinoma with the GGO radiographic presentation. Multidisciplinary discussion confirmed the need for surgery in all cases. We used an age and gender‐matched group without known lung disease as a control. Telomere length and aggregates were assessed by quantitative fluorescence in situ hybridization (QFISH) and quantitative PCR. Cell senescence was evaluated by senescence‐associated heterochromatin foci. Subjects with GGO lesions had a higher percentage of lymphocytes with shorter telomeres (Q‐FISH, P = 0.003). Furthermore, relative telomere length was also reduced among the GGO cases (qPCR, P < 0.05). Increased senescence was observed in the GGO group compared to controls (P < 0.001), with significant correlation between the senescence‐associated heterochromatin foci and aggregate formation (r = −0.7 and r = −0.44 for cases and controls, respectively). In conclusion, patients with resectable early adenocarcinoma demonstrate abnormal telomere length and cell senescence in peripheral blood leukocytes compared to control subjects. Abnormal telomere biology in the peripheral blood may increase suspicion of early adenocarcinoma among patients with GGO lesions.

Published
2019
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17. Hypoglycaemia symptom frequency, severity, burden, and utility among adults with type 1 diabetes and impaired awareness of hypoglycaemia: Baseline and 24‐week findings from the HypoCOMPaSS study

Author

Søholm, Uffe, primary, Holmes‐Truscott, Elizabeth, additional, Broadley, Melanie, additional, Amiel, Stephanie A., additional, Hendrieckx, Christel, additional, Choudhary, Pratik, additional, Pouwer, Frans, additional, Shaw, James A. M., additional, and Speight, Jane, additional

Published
2023
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21. Two novel variations p.( <scp>Ser1275Thr</scp> ) and p.( <scp>Ser1275Arg</scp> ) in <scp> FLT4 </scp> causing prenatal hereditary lymphedema type 1

Author

Yosra Lajmi, Laurence Loeuillet, Giulia Petrilli, Charles Egloff, Juliette Nectoux, Clémence Molac, Nathalie Roux, Emmanuelle Pannier, Amale Achaiaa, Zaina Ait Arkoub, Sophie Chuon, Aurélie Coussement, Jean Michel Dupont, Valérie Malan, Emmanuel Spaggiari, Ferechte Razavi, Jeanne Amiel, Bettina Bessières, Sarah Grotto, and Tania Attié‐Bitach

Subjects
Embryology, Health, Toxicology and Mutagenesis, Pediatrics, Perinatology and Child Health, Toxicology, Developmental Biology
Published
2022
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22. Low risk of embryonic and other cancers in PIK3CA‐related overgrowth spectrum: Impact on screening recommendations

Author

Faivre, Laurence, primary, Crépin, Jean‐Charles, additional, Réda, Manon, additional, Nambot, Sophie, additional, Carmignac, Virginie, additional, Abadie, Caroline, additional, Mirault, Tristan, additional, Faure‐Conter, Cécile, additional, Mazereeuw‐Hautier, Juliette, additional, Maza, Aude, additional, Puzenat, Eve, additional, Collonge‐Rame, Marie‐Agnès, additional, Bursztejn, Anne‐Claire, additional, Philippe, Christophe, additional, Thauvin‐Robinet, Christel, additional, Chevarin, Martin, additional, Abasq‐Thomas, Claire, additional, Amiel, Jeanne, additional, Arpin, Stéphanie, additional, Barbarot, Sébastien, additional, Baujat, Geneviève, additional, Bessis, Didier, additional, Bourrat, Emmanuelle, additional, Boute, Odile, additional, Chassaing, Nicolas, additional, Coubes, Christine, additional, Demeer, Bénédicte, additional, Edery, Patrick, additional, El Chehadeh, Salima, additional, Goldenberg, Alice, additional, Hadj‐Rabia, Smail, additional, Haye, Damien, additional, Isidor, Bertrand, additional, Jacquemont, Marie‐Line, additional, Van Kien, Philippe Khau, additional, Lacombe, Didier, additional, Lehalle, Daphné, additional, Lambert, Laetitia, additional, Martin, Ludovic, additional, Maruani, Annabel, additional, Morice‐Picard, Fanny, additional, Petit, Florence, additional, Phan, Alice, additional, Pinson, Lucile, additional, Rossi, Massimiliano, additional, Touraine, Renaud, additional, Vanlerberghe, Clémence, additional, Vincent, Marie, additional, Vincent‐Delorme, Catherine, additional, Whalen, Sandra, additional, Willems, Marjolaine, additional, Marle, Nathalie, additional, Verkarre, Virginie, additional, Devalland, Christine, additional, Devouassoux‐Shisheboran, Mojgan, additional, Abad, Marine, additional, Rioux‐Leclercq, Nathalie, additional, Bonniaud, Bertille, additional, Duffourd, Yannis, additional, Martel, Jehanne, additional, Binquet, Christine, additional, Kuentz, Paul, additional, and Vabres, Pierre, additional

Published
2023
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23. A phase 2 study of ibrutinib maintenance following first‐line high‐dose methotrexate‐based chemotherapy for elderly patients with primary central nervous system lymphoma

Author

Bairey, Osnat, primary, Taliansky, Alisa, additional, Glik, Amir, additional, Amiel, Alexandra, additional, Yust‐Katz, Shlomit, additional, Gurion, Ronit, additional, Zektser, Miri, additional, Porges, Tzvika, additional, Sarid, Nadav, additional, Horowitz, Netanel A., additional, Shina, Tzahala Tzuk, additional, Lebel, Eyal, additional, Cohen, Amos, additional, Geiger, Karyn Revital, additional, Raanani, Pia, additional, Wolach, Ofir, additional, and Siegal, Tali, additional

Published
2023
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24. Broadening the phenotypic spectrum of <scp>EVEN‐PLUS</scp> syndrome through identification of <scp> HSPA9 </scp> pathogenic variants in the original <scp>EVE</scp> dysplasia family and two sibs with milder facial phenotype

Author

Marta Pacio‐Miguez, Manuel Parrón‐Pajares, Christopher T. Gordon, Fernando Santos‐Simarro, Carmen Rodríguez Jiménez, Rocio Mena, Inmaculada Rueda Arenas, Victoria Eugenia F. Montaño, María Fernández, Mario Solís, Ángela del Pozo, Jeanne Amiel, Sixto García‐Miñaur, and María Palomares‐Bralo

Subjects
Genetics, Genetics (clinical)
Published
2022
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25. Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol

Author

Divilly, Patrick, Zaremba, Natalie, Mahmoudi, Zeinab, Søholm, Uffe, Pollard, Daniel J, Broadley, Melanie, Abbink, Evertine J, De Galan, Bastiaan, Pedersen-Bjergaard, Ulrik, Renard, Eric, Evans, Mark, Speight, Jane, Brennan, Alan, McCrimmon, Rory J, Müllenborn, Matthias, Heller, Simon, Seibold, Alexander, Mader, Julia K, Amiel, Stephanie A, Pouwer, Frans, Choudhary, Pratik, Hypo-RESOLVE Consortium, Divilly, Patrick [0000-0001-6916-3164], Zaremba, Natalie [0000-0002-1720-1621], Mahmoudi, Zeinab [0000-0001-9426-1962], Søholm, Uffe [0000-0003-0848-9421], Pollard, Daniel J [0000-0001-5630-0115], Broadley, Melanie [0000-0003-4408-6304], de Galan, Bastiaan [0000-0002-1255-7741], Pedersen-Bjergaard, Ulrik [0000-0003-0588-4880], Evans, Mark [0000-0001-8122-8987], Speight, Jane [0000-0002-1204-6896], Brennan, Alan [0000-0002-1025-312X], McCrimmon, Rory J [0000-0002-3957-1981], Müllenborn, Matthias [0000-0003-3947-4695], Heller, Simon [0000-0002-2425-9565], Seibold, Alexander [0000-0002-2008-4593], Mader, Julia K [0000-0001-7854-4233], Amiel, Stephanie A [0000-0003-2686-5531], Pouwer, Frans [0000-0002-8172-9818], Choudhary, Pratik [0000-0001-7635-4735], and Apollo - University of Cambridge Repository

Subjects
Blood Glucose, Glycated Hemoglobin, endocrine system diseases, Blood Glucose Self-Monitoring, nutritional and metabolic diseases, Hypoglycemia, sensor-detected, Benchmarking, Observational Studies as Topic, Diabetes Mellitus, Type 1, quality of life, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, continuous glucose monitoring, patient-reported hypoglycaemia, hypoglycaemia
Abstract

INTRODUCTION: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. METHODS: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. ETHICS AND DISSEMINATION: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations., Hypo-RESOLVE has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777460

Published
2022

26. Association between early change in neutrophil‐to‐lymphocyte ratio after radical cystectomy and treatment outcomes

Author

Haim Herzberg, Karin Lifshitz, Shay Golan, Jack Baniel, Kamil Malshy, Azik Hoffman, Gilad E. Amiel, Rani Zreik, Yuval Freifeld, Yoram Dekel, Rinat Lasmanovich, Alon Lazarovich, Barak Rosenzweig, Zohar Dotan, Ofer Yossepowitch, and Roy Mano

Subjects
Treatment Outcome, Urinary Bladder Neoplasms, Neutrophils, Urology, Humans, Lymphocyte Count, Lymphocytes, Neoplasm Recurrence, Local, Cystectomy, Prognosis, Disease-Free Survival, Aged, Retrospective Studies
Abstract

To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy.We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival.The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004).Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Published
2022
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27. Toward clinical and molecular dissection of frontonasal dysplasia with facial skin polyps: From Pai syndrome to differential diagnosis through a series of 27 patients

Author

Daphné Lehalle, Ange‐Line Bruel, Antonio Vitobello, Anne‐Sophie Denommé‐Pichon, Yannis Duffourd, Mirna Assoum, Jeanne Amiel, Geneviève Baujat, Bettina Bessieres, Stefania Bigoni, Lydie Burglen, Guillaume Captier, Rodolphe Dard, Patrick Edery, Fernanda Fortunato, David Geneviève, Alice Goldenberg, Laurent Guibaud, Delphine Héron, Muriel Holder‐Espinasse, Damien Lederer, Fermina Lopez Grondona, Sarah Grotto, Sandrine Marlin, Gwenaël Nadeau, Arnaud Picard, Massimiliano Rossi, Joëlle Roume, Damien Sanlaville, Pascale Saugier‐Veber, Stéphane Triau, Maria Irene Valenzuela Palafoll, Clémence Vanlerberghe, Lionel Van Maldergem, Myriam Vezain, Catherine Vincent‐Delorme, Einat Zivi, Julien Thevenon, Pierre Vabres, Christel Thauvin‐Robinet, Patrick Callier, and Laurence Faivre

Subjects
Eye Diseases, Cleft Lip, Neurocutaneous Syndromes, Skin Diseases, Spine, Coloboma, Craniofacial Abnormalities, Diagnosis, Differential, Nasal Polyps, Face, Genetics, Humans, Lipomatosis, Eye Abnormalities, Lipoma, Agenesis of Corpus Callosum, Ear, External, Respiratory System Abnormalities, Genetics (clinical)
Abstract

Unique or multiple congenital facial skin polyps are features of several rare syndromes, from the most well-known Pai syndrome (PS), to the less recognized oculoauriculofrontonasal syndrome (OAFNS), encephalocraniocutaneous lipomatosis (ECCL), or Sakoda complex (SC). We set up a research project aiming to identify the molecular bases of PS. We reviewed 27 individuals presenting with a syndromic frontonasal polyp and initially referred for PS. Based on strict clinical classification criteria, we could confirm only nine (33%) typical and two (7%) atypical PS individuals. The remaining ones were either OAFNS (11/27-41%) or presenting with an overlapping syndrome (5/27-19%). Because of the phenotypic overlap between these entities, OAFNS, ECCL, and SC can be either considered as differential diagnosis of PS or part of the same spectrum. Exome and/or genome sequencing from blood DNA in 12 patients and from affected tissue in one patient failed to identify any replication in candidate genes. Taken together, our data suggest that conventional approaches routinely utilized for the identification of molecular etiologies responsible for Mendelian disorders are inconclusive. Future studies on affected tissues and multiomics studies will thus be required in order to address either the contribution of mosaic or noncoding variation in these diseases.

Published
2022
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28. First evidence of <scp> SOX2 </scp> mutations in Peters' anomaly: Lessons from molecular screening of 95 patients

Author

Bertrand Chesneau, Marion Aubert‐Mucca, Félix Fremont, Jacmine Pechmeja, Vincent Soler, Bertrand Isidor, Mathilde Nizon, Hélène Dollfus, Josseline Kaplan, Lucas Fares‐Taie, Jean‐Michel Rozet, Tiffany Busa, Didier Lacombe, Sophie Naudion, Jeanne Amiel, Marlène Rio, Tania Attie‐Bitach, Cécile Lesage, Dominique Thouvenin, Sylvie Odent, Godelieve Morel, Catherine Vincent‐Delorme, Odile Boute, Clémence Vanlerberghe, Anne Dieux, Simon Boussion, Laurence Faivre, Lucile Pinson, Fanny Laffargue, Gwenaël Le Guyader, Guylène Le Meur, Fabienne Prieur, Victor Lambert, Beatrice Laudier, Edouard Cottereau, Carmen Ayuso, Marta Corton‐Pérez, Laurence Bouneau, Cédric Le Caignec, Véronique Gaston, Claire Jeanton‐Scaramouche, Delphine Dupin‐Deguine, Patrick Calvas, Nicolas Chassaing, Julie Plaisancié, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut des Jeunes Aveugles [Toulouse] (IJA), Clinique rive gauche, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de référence Maladies Rares CLAD-Ouest [Rennes], CHU Lille, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département génétique méd, mal rares et médecine personnalisée [CHRU de Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional d'Orléans (CHRO), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIBER de Enfermedades Raras (CIBERER), Universidad Autónoma de Madrid (UAM), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), French National Research AgencyFrench National Research Agency (ANR) [ANR-10-COHO-0003], and ANR-10-COHO-0003,RADICO,Cohorte nationale maladies rares(2010)

Subjects
Comparative Genomic Hybridization, [SDV.GEN]Life Sciences [q-bio]/Genetics, DNA Copy Number Variations, SOXB1 Transcription Factors, Peters' anomaly, [SDV]Life Sciences [q-bio], CNV, SOX2, eye diseases, PAX6, Corneal Opacity, microphthalmia, Anterior Eye Segment, Mutation, B3GLCT, Genetics, Humans, anterior segment dysgenesis, FOXE3, Eye Abnormalities, PITX3, Genetics (clinical)
Abstract

International audience; Peters' anomaly (PA) is a rare anterior segment dysgenesis characterized by central corneal opacity and irido-lenticulo-corneal adhesions. Several genes are involved in syndromic or isolated PA (B3GLCT, PAX6, PITX3, FOXE3, CYP1B1). Some copy number variations (CNVs) have also been occasionally reported. Despite this genetic heterogeneity, most of patients remain without genetic diagnosis. We retrieved a cohort of 95 individuals with PA and performed genotyping using a combination of comparative genomic hybridization, whole genome, exome and targeted sequencing of 119 genes associated with ocular development anomalies. Causative genetic defects involving 12 genes and CNVs were identified for 1/3 of patients. Unsurprisingly, B3GLCT and PAX6 were the most frequently implicated genes, respectively in syndromic and isolated PA. Unexpectedly, the third gene involved in our cohort was SOX2, the major gene of micro-anophthalmia. Four unrelated patients with PA (isolated or with microphthalmia) were carrying pathogenic variants in this gene that was never associated with PA before. Here we described the largest cohort of PA patients ever reported. The genetic bases of PA are still to be explored as genetic diagnosis was unavailable for 2/3 of patients. Nevertheless, we showed here for the first time the involvement of SOX2 in PA, offering new evidence for its role in corneal transparency and anterior segment development.

Published
2022
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29. An automatic facial landmarking for children with rare diseases

Author

Hennocq, Quentin, primary, Bongibault, Thomas, additional, Bizière, Matthieu, additional, Delassus, Ombline, additional, Douillet, Maxime, additional, Cormier‐Daire, Valérie, additional, Amiel, Jeanne, additional, Lyonnet, Stanislas, additional, Marlin, Sandrine, additional, Rio, Marlène, additional, Picard, Arnaud, additional, Khonsari, Roman Hossein, additional, and Garcelon, Nicolas, additional

Published
2023
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30. Post‐HCV cure self‐reported changes in physical activity, eating behaviours, and fatigue in people living with HIV (ANRS CO13 HEPAVIH)

Author

Marcellin, Fabienne, Di Beo, Vincent, Esterle, Laure, Abgrall, Sophie, Pialoux, Gilles, Barré, Tangui, Wittkop, Linda, Salmon‐ceron, Dominique, Sogni, Philippe, Carrieri, Patrizia, Roustant, F, Platterier, P, Kmiec, I, Traore, L, Lepuil, S, Parlier, S, Sicart‐payssan, V, Bedel, E, Anriamiandrisoa, S, Pomes, C, Mole, M, Bolliot, C, Catalan, P, Mebarki, M, Adda‐lievin, A, Thilbaut, P, Ousidhoum, Y, Makhoukhi, F.Z, Braik, O, Bayoud, R, Gatey, C, Pietri, M.P, Le Baut, V, Ben Rayana, R, Bornarel, D, Chesnel, C, Beniken, D, Pauchard, M, Akel, S, Lions, C, Ivanova, A, Ritleg, A‐s, Debreux, C, Chalal, L, Zelie, J, Hue, H, Soria, A, Cavellec, M, Breau, S, Joulie, A, Fisher, P, Gohier, S, Croisier‐bertin, D, Ogoudjobi, S, Brochier, C, Thoirain‐galvan, V, Le Cam, M, Chalouni, M, Conte, V, Dequae‐merchadou, L, Desvallees, M, Gilbert, C, Gillet, S, Knight, R, Lemboub, T, Michel, L, Mora, M, Protopopescu, C, Roux, P, Tezkratt, S, Ramier, C, Sow, A, Bureau, M, Trimoulet, P, Izopet, J, Serfaty, L, Paradis, V, Spire, B, Valantin, V., Chas, J, Zaegel‐faucher, O, Barange, K, Naqvi, A, Rosenthal, E, Bicart‐see, A, Bouchaud, O, Gervais, A, Lascoux‐combe, C, Goujard, C, Lacombe, K, Duvivier, C, Neau, D, Morlat, P, Bani‐sadr, F, Meyer, L, Boufassa, F, Autran, B, Roque, A.M, Solas, C, Fontaine, H, Costagliola, D, Piroth, L, Simon, A, Zucman, D, Boué, F, Miailhes, P, Billaud, E, Aumaître, H, Rey, D, Peytavin, G, Petrov‐sanchez, V, Levier, A, Usubillaga, R., Terris, B, Tremeaux, P, Katlama, C, Stitou, H, Cacoub, P, Nafissa, S, Benhamou, Y, Charlotte, F, Fourati, S, Poizot‐martin, I, Zaegel, O, Laroche, H, Tamalet, C, Callard, P, Bendjaballah, F, Amiel, C, Le Pendeven, C, Marchou, B, Alric, L, Metivier, S, Selves, J, Larroquette, F, Rio, V, Haudebourg, J, Saint‐paul, M.C, de Monte, A, Giordanengo, V, Partouche, C, Martin, A, Ziol, M, Baazia, Y, Iwaka‐bande, V, Gerber, A, Uzan, M, Garipuy, D, Ferro‐collados, M.J, Nicot, F, Yazdanpanah, Y, Adle‐biassette, H, Alexandre, G, Molina, J.M, Bertheau, P, Chaix, M.L, Delaugerre, C, Maylin, S, Bottero, J, Krause, J, Girard, P.M, Wendum, D, Cervera, P, Adam, J, Viala, C, Vittecocq, D, Quertainmont, Y, Teicher, E, Pallier, C, Lortholary, O, Rouzaud, C, Lourenco, J, Touam, F, Louisin, C, Avettand‐fenoel, V, Gardiennet, E, Mélard, A, Ochoa, A, Blanchard, E, Castet‐lafarie, S, Cazanave, C, Malvy, D, Dupon, M, Dutronc, H, Dauchy, F, Lacaze‐buzy, L, Desclaux, A, Bioulac‐sage, P, Reigadas, S, Lacoste, D, Bonnet, F, Bernard, N, Hessamfar, M, Paccalin, J.F, Martell, C, Pertusa, M.C, Vandenhende, M, Mercié, P, Pistone, T, Receveur, M.C, Méchain, M, Duffau, P, Rivoisy, C, Faure, I, Caldato, S, Bellecave, P, Tumiotto, C, Pellegrin, J.L, Viallard, J.F, Lazzaro, E, Greib, C, Majerholc, C, Brollo, M, Farfour, E, Polo Devoto, J, Kansau, I, Chambrin, V, Pignon, C, Berroukeche, L, Fior, R, Martinez, V, Favier, M, Deback, C, Lévy, Y, Dominguez, S, Lelièvre, J.D, Lascaux, A.S, Melica, G, Raffi, F, Allavena, C, Reliquet, V, Boutoille, D, Biron, C, Lefebvre, M, Hall, N, Bouchez, S, Rodallec, A, Le Guen, L, Hemon, C, Peyramond, D, Chidiac, C, Ader, F, Biron, F, Boibieux, A, Cotte, L, Ferry, T, Perpoint, T, Koffi, J, Zoulim, F, Bailly, F, Lack, P, Maynard, M, Radenne, S, Amiri, M, Valour, F, Augustin‐normand, C, Scholtes, C, Le‐thi, T.T, Chavanet, P, Duong van Huyen, M, Buisson, M, Waldner‐combernoux, A, Mahy, S, Salmon Rousseau, A, Martins, C, Galim, S, Lambert, D, Nguyen, Y, Berger, J.L, Hentzien, M, Brodard, V, Partisani, M, Batard, M.L, Cheneau, C, Priester, M, Bernard‐henry, C, de Mautort, E, Fischer, P, Gantner, P, Fafi‐kremer, S, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences de la santé publique [Marseille] (ISSPAM), Team MORPH3EUS (INSERM U1219 - UB - ISPED), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), ANRS CO13 HEPAVIH Study Group: F Roustant, P Platterier, I Kmiec, L Traore, S Lepuil, S Parlier, V Sicart-Payssan, E Bedel, S Anriamiandrisoa, C Pomes, M Mole, C Bolliot, P Catalan, M Mebarki, A Adda-Lievin, P Thilbaut, Y Ousidhoum, F Z Makhoukhi, O Braik, R Bayoud, C Gatey, M P Pietri, V Le Baut, R Ben Rayana, D Bornarel, C Chesnel, D Beniken, M Pauchard, S Akel, C Lions, A Ivanova, A-S Ritleg, C Debreux, L Chalal, J Zelie, H Hue, A Soria, M Cavellec, S Breau, A Joulie, P Fisher, S Gohier, D Croisier-Bertin, S Ogoudjobi, C Brochier, V Thoirain-Galvan, M Le Cam, M Chalouni, V Conte, L Dequae-Merchadou, M Desvallees, C Gilbert, S Gillet, R Knight, T Lemboub, L Michel, M Mora, C Protopopescu, P Roux, S Tezkratt, C Ramier, A Sow, M Bureau, P Trimoulet, J Izopet, L Serfaty, V Paradis, B Spire, Valantin, J Chas, O Zaegel-Faucher, K Barange, A Naqvi, E Rosenthal, A Bicart-See, O Bouchaud, A Gervais, C Lascoux-Combe, C Goujard, K Lacombe, C Duvivier, D Neau, P Morlat, F Bani-Sadr, L Meyer, F Boufassa, B Autran, A M Roque, C Solas, H Fontaine, D Costagliola, L Piroth, A Simon, D Zucman, F Boué, P Miailhes, E Billaud, H Aumaître, D Rey, G Peytavin, V Petrov-Sanchez, A Levier, R Usubillaga, B Terris, P Tremeaux, C Katlama, H Stitou, P Cacoub, S Nafissa, Y Benhamou, F Charlotte, S Fourati, I Poizot-Martin, O Zaegel, H Laroche, C Tamalet, P Callard, F Bendjaballah, C Amiel, C Le Pendeven, B Marchou, L Alric, S Metivier, J Selves, F Larroquette, V Rio, J Haudebourg, M C Saint-Paul, A De Monte, V Giordanengo, C Partouche, A Martin, M Ziol, Y Baazia, V Iwaka-Bande, A Gerber, M Uzan, D Garipuy, M J Ferro-Collados, J Selves, F Nicot, Y Yazdanpanah, H Adle-Biassette, G Alexandre, J M Molina, P Bertheau, M L Chaix, C Delaugerre, S Maylin, J Bottero, J Krause, P M Girard, D Wendum, P Cervera, J Adam, C Viala, D Vittecocq, Y Quertainmont, E Teicher, C Pallier, O Lortholary, C Rouzaud, J Lourenco, F Touam, C Louisin, V Avettand-Fenoel, E Gardiennet, A Mélard, A Ochoa, E Blanchard, S Castet-Lafarie, C Cazanave, D Malvy, M Dupon, H Dutronc, F Dauchy, L Lacaze-Buzy, A Desclaux, P Bioulac-Sage, S Reigadas, D Lacoste, F Bonnet, N Bernard, M Hessamfar, J F Paccalin, C Martell, M C Pertusa, M Vandenhende, P Mercié, D Malvy, T Pistone, M C Receveur, M Méchain, P Duffau, C Rivoisy, I Faure, S Caldato, P Bioulac-Sage, S Reigadas, P Bellecave, C Tumiotto, J L Pellegrin, J F Viallard, E Lazzaro, C Greib, P Bioulac-Sage, S Reigadas, C Majerholc, M Brollo, E Farfour, J Polo Devoto, I Kansau, V Chambrin, C Pignon, L Berroukeche, R Fior, V Martinez, M Favier, C Deback, Y Lévy, S Dominguez, J D Lelièvre, A S Lascaux, G Melica, F Raffi, C Allavena, V Reliquet, D Boutoille, C Biron, M Lefebvre, N Hall, S Bouchez, A Rodallec, L Le Guen, C Hemon, D Peyramond, C Chidiac, F Ader, F Biron, A Boibieux, L Cotte, T Ferry, T Perpoint, J Koffi, F Zoulim, F Bailly, P Lack, M Maynard, S Radenne, M Amiri, F Valour, J Koffi, F Zoulim, F Bailly, P Lack, M Maynard, S Radenne, C Augustin-Normand, C Scholtes, T T Le-Thi, P Chavanet, M Duong Van Huyen, M Buisson, A Waldner-Combernoux, S Mahy, A Salmon Rousseau, C Martins, S Galim, D Lambert, Y Nguyen, J L Berger, M Hentzien, V Brodard, M Partisani, M L Batard, C Cheneau, M Priester, C Bernard-Henry, E de Mautort, P Fischer, P Gantner, S Fafi-Kremer, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), and Malbec, Odile

Subjects
0303 health sciences, Hepatology, business.industry, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), MEDLINE, Physical activity, medicine.disease_cause, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Virology, Medicine, 030211 gastroenterology & hepatology, business, Eating behaviour, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Clinical psychology
Abstract

International audience; No abstract available

Published
2021
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31. Two novel variations p.( Ser1275Thr ) and p.( Ser1275Arg ) inFLT4causing prenatal hereditary lymphedema type 1

Author

Lajmi, Yosra, primary, Loeuillet, Laurence, additional, Petrilli, Giulia, additional, Egloff, Charles, additional, Nectoux, Juliette, additional, Molac, Clémence, additional, Roux, Nathalie, additional, Pannier, Emmanuelle, additional, Achaiaa, Amale, additional, Arkoub, Zaina Ait, additional, Chuon, Sophie, additional, Coussement, Aurélie, additional, Dupont, Jean Michel, additional, Malan, Valérie, additional, Spaggiari, Emmanuel, additional, Razavi, Ferechte, additional, Amiel, Jeanne, additional, Bessières, Bettina, additional, Grotto, Sarah, additional, and Attié‐Bitach, Tania, additional

Published
2022
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36. Retrospective evaluation of clinical and molecular data of 148 cases of esophageal atresia

Author

Ranza, Emmanuelle, primary, Le Gouez, Morgane, additional, Guimier, Anne, additional, Dunlop, Naziha Khen, additional, Beaudoin, Sylvie, additional, Malan, Valérie, additional, Michot, Caroline, additional, Baujat, Geneviève, additional, Rio, Marlène, additional, Cormier‐Daire, Valérie, additional, Abadie, Véronique, additional, Sarnacki, Sabine, additional, Delacourt, Christophe, additional, Lyonnet, Stanislas, additional, Attié‐Bitach, Tania, additional, Pingault, Véronique, additional, Rousseau, Véronique, additional, and Amiel, Jeanne, additional

Published
2022
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37. Inflammasome activation in preeclampsia and intrauterine growth restriction

Author

Michal Silber, Nadav Dekel, Ishai Heusler, Tal Biron‐Shental, Aliza Amiel, Debora Kidron, Avivit Weisz, Sydney Benchetrit, and Tali Zitman‐Gal

Subjects
Fetal Growth Retardation, Inflammasomes, Placenta, Immunology, Infant, Newborn, Endothelial Cells, Obstetrics and Gynecology, Pre-Eclampsia, Reproductive Medicine, Pregnancy, Humans, Immunology and Allergy, Female, Prospective Studies, Adaptor Proteins, Signal Transducing
Abstract

Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR.In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery.NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples vs. NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood.NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR. This article is protected by copyright. All rights reserved.

Published
2022
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41. Broadening the phenotypic spectrum of EVEN‐PLUS syndrome through identification of HSPA9 pathogenic variants in the original EVE dysplasia family and two sibs with milder facial phenotype

Author

Pacio‐Miguez, Marta, primary, Parrón‐Pajares, Manuel, additional, Gordon, Christopher T., additional, Santos‐Simarro, Fernando, additional, Rodríguez Jiménez, Carmen, additional, Mena, Rocio, additional, Rueda Arenas, Inmaculada, additional, F. Montaño, Victoria Eugenia, additional, Fernández, María, additional, Solís, Mario, additional, del Pozo, Ángela, additional, Amiel, Jeanne, additional, García‐Miñaur, Sixto, additional, and Palomares‐Bralo, María, additional

Published
2022
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42. Concordance testing between Powerplex ESI 16 Fast System and VeriFiler Express

Author

Ortal Waiskopf, Hagit Schayek, Orna Avlas, Merav Amiel, Ehud Wolf, and Ksenia Rashkovski

Subjects
Genetics, Dna template, Genotype, Concordance, 010401 analytical chemistry, Biology, DNA Fingerprinting, 01 natural sciences, 0104 chemical sciences, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, DNA profiling, DNA database, Humans, 030216 legal & forensic medicine, Allele, Genotyping, Inbreeding, Alleles, Microsatellite Repeats
Abstract

DNA profiles generated by different STR kits may show different alleles for identical amplified loci. This well-known phenomenon affects the smooth transition of data generated by new STR kits to a database or casework laboratory or cross-laboratory comparison of STR profiles. As in other DNA databases throughout the world, it has become clear that the number of the analyzed loci should be expanded for a variety of reasons, such as partial profiles resulting from low copy-number DNA template or degraded samples, working with mixtures or when prevalence of familial inbreeding. In the course of introducing a new STR kit, VeriFiler™ Express (Applied Biosystems, Foster City, CA, USA), we compared genotyping data of 1568 samples amplified by the VeriFiler™ Express with the data generated on the same samples by the Powerplex™ ESI FAST (Promega, Madison WI, USA) kit. Discordance was noted in 20 samples (1.27%), 14 (0.89%) of them showing allele dropout mismatch and six (0.38%) showing an additional fixed-size third allele. These rates are well above the reported rates of 0.4% for this kit. Since correct genotyping and accurate consistent allele assignment is of paramount importance, it seems timely to recommend for DNA laboratories and genetic-match search systems to take these possible inconsistencies into account.

Published
2020
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43. Clinical Characteristics and Outcome of Drug‐Induced Liver Injury in the Older Patients: From the Young‐Old to the Oldest‐Old

Author

Rianne A. Weersink, Ismael Alvarez‐Alvarez, Inmaculada Medina‐Cáliz, Judith Sanabria‐Cabrera, Mercedes Robles‐Díaz, Aida Ortega‐Alonso, Miren García‐Cortés, Elvira Bonilla, Hao Niu, German Soriano, Miguel Jimenez‐Perez, Hacibe Hallal, Sonia Blanco, Neil Kaplowitz, M. Isabel Lucena, Raúl J. Andrade, R.J. Andrade, M.I. Lucena, C. Stephens, M. García Cortés, M. Robles Díaz, A. Ortega Alonso, J. Pinazo, B. García Muñoz, R. Alcántara, A. Hernández, M.D. García‐Escaño, I. Medina‐Cáliz, J. Sanabria‐Cabrera, I. Alvarez‐Alvarez, E. Bonilla, H. Niu, D. Di‐Zeo, E. Del Campo, M. Jiménez Pérez, R. González Grande, S. López Ortega, I. Santaella, A. Ocaña, P. Palomino, M.C. Fernández, A. Porcel, M. Casado, M. González Sánchez, M. Romero‐Gómez, R. Millán‐Domínguez, B. Fombuena, R. Gallego, J. Ampuero, J.A. del Campo, R. Calle‐Sanz, L. Rojas, A. Rojas, A. Gil Gómez, E. Vilar, G. Soriano, C. Guarner, E.M. Román, M.A. Quijada Manuitt, R.M. Antonijoan Arbos, M. Farré, E. Montané, A.L. Arellano, A.M. Barriocanal, Y. Sanz, R.M. Morillas, M. Sala, H. Masnou Ridaura, J. Sánchez Delgado, M. Vergara Gómez, H. Hallal, E. García Oltra, J.C. Titos Arcos, A. Pérez Martínez, C. Sánchez Cobarro, J.M. Egea Caparrós, A. Castiella, J. Arenas, M.I. Gomez Osua, A. Gómez García, F.J. Esandi, S. Blanco, P. Martínez Odriozola, J. Crespo, P. Iruzubieta, J. Cabezas, A. Giráldez Gallego, E. del P. Rodríguez Seguel, M. Cuaresma, M. Prieto, I. Conde Amiel, M. Berenguer, M. García‐Eliz, J.M. Moreno, P. Martínez‐Rodenas, M. Garrido, C. Oliva, E. Gómez Domínguez, L. Cabrera, L. Cuevas, M. Bruguera, P. Gines, S. Lens, J.C. García, Z. Mariño, M. Hernández Guerra, M. Moreno San Fiel, C. Boada Fernández del Campo, J. Fuentes Olmo, E.M. Fernández Bonilla, F. Jorquera, and J. González Gallego

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Hígado - Enfermedades, Comorbidity, elderly, Severity of Illness Index, 030226 pharmacology & pharmacy, Culprit, oldest-old, Young Adult, 03 medical and health sciences, Liver disease, Sex Factors, 0302 clinical medicine, Levofloxacin, Internal medicine, medicine, Humans, Pharmacology (medical), Ticlopidine, Child, Aged, Aged, 80 and over, Pharmacology, Polypharmacy, business.industry, Age Factors, Odds ratio, Middle Aged, Jaundice, medicine.disease, mortality, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Spain, 030220 oncology & carcinogenesis, comorbitity, Female, Chemical and Drug Induced Liver Injury, medicine.symptom, business, drug-induced liver injury, Cholestatic, medicine.drug
Abstract

Old patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought for the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% ≥65 years) were categorized according to age: “young” (

Published
2020
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44. Association between PSA density and pathologically significant prostate cancer: The impact of prostate volume

Author

Sabo Edmond, Kakiashvili David, Hoffman Azik, Kravtzov Alexander, Kastin Alexander, Amiel Gilad, Zisman Ariel, Nativ Omri, and Malshy Kamil

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Urology, Pathological staging, medicine.medical_treatment, Psa density, urologic and male genital diseases, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, medicine, Humans, Registries, Early Detection of Cancer, Aged, Digital Rectal Examination, Ultrasonography, Aged, 80 and over, Prostatectomy, medicine.diagnostic_test, business.industry, Prostatic Neoplasms, Organ Size, Rectal examination, Middle Aged, Prostate-Specific Antigen, Prognosis, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cohort, Neoplasm Grading, business, Body mass index
Abstract

Background The early diagnosis of prostate cancer (PCa) is mainly based on prostate-specific antigen (PSA) blood levels and digital rectal examination. However, this approach may result in a high rate of negative biopsies and increased detection of clinically insignificant PCa (CS-PCa). An important prognostic biomarker, PSA density (PSA-D) demonstrated improved performance in PCa detection compared to PSA. The relationship between prostate volume and the prognostic accuracy of PSA-D remains mostly unclear. The aim of our study is to investigate the PSA-D predictive value of CS-PCa detection at different prostate volumes. Methods Using our local radical prostatectomy registry, patients were divided into three prostate size subgroups based on preoperative sonographic prostate volume assessment: less than 50, 50-75, and more than 75 cc. Patients' and PCa characteristics were recorded, including age, body mass index, PSA at diagnosis, prostate volume, PSA-D, D'Amico risk classification, Gleason grade group, and pathological staging following surgery. Results The study cohort included 364 patients who underwent Robotic Radical prostatectomy for biopsy-proven clinically localized PCa. 221 (61%) and 143 (39%) patients had PSA-D less than 0.15 and PSA-D more than 0.15, respectively. ISUP GG 1-2 PCa (CS-PCa) was observed in 220 patients (60%), while 144 (40%) had ISUP GG 3-5 PCa at final pathology. PSA-D correlated with CS-PCa only in small and medium-size prostates, but not in large glands (p = .03, p = .01, and p = .36, respectively). The highest sensitivity (72.7%) was observed in small prostates, compared to 3.2% in large prostates. The highest specificity (89.4%) was noted in large prostates. Positive predictive value in small and medium-size prostates was similar (~50%), compared to 20% in large glands. The negative predictive value was slightly better for small and medium-size prostates compared with large glands (68.9%, 73.7%, and 53.1%, respectively). An association between PSA-D and harboring CS-PCa was detected only in small and medium-size glands (72.7% and 43%, respectively). Conclusion PSA-D is associated with CS-PCa detection in radical prostatectomy specimens in small and medium-size prostates. The level of PSA-D is directly associated with the ISUP PCa grade group. Therefore, PSA-D is a beneficial, available, and cost-effective tool during decision-making in patients with small and medium-size prostate when considering treatment for PCa.

Published
2020
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45. Activating variants in <scp> PDGFRB </scp> result in a spectrum of disorders responsive to imatinib monotherapy

Author

Richard Webster, Meredith Wilson, Joseph T. Shieh, Deepti Gupta, Carrie L. Heike, Elizabeth J. Bhoj, David B. Everman, John P. Dahl, Hakon Hakonarson, Yuri A. Zarate, Anne Guimier, Danny E. Miller, Margaret P. Adam, Anita E. Beck, Shireen Ganapathi, Catherine M. Albert, Angela Sun, Dong Li, Tara L. Wenger, Irene Chang, Natalie Wu, Markus D. Boos, John Christodoulou, Elaine H. Zackai, Randall A. Bly, Jirat Chenbhanich, Jeanne Amiel, Cynthia J. Curry, Julie Park, William B. Dobyns, and Jonathan A. Perkins

Subjects
Adult, Male, Oncology, Premature aging, medicine.medical_specialty, Adolescent, Infantile myofibromatosis, PDGFRB, Disease, Sudden death, Receptor, Platelet-Derived Growth Factor beta, Leukoencephalopathies, Internal medicine, Genetics, Humans, Medicine, Child, Protein Kinase Inhibitors, Genetic Association Studies, Genetics (clinical), business.industry, Infant, Myofibromatosis, Imatinib, medicine.disease, Aneurysm, Pedigree, Imatinib mesylate, Overgrowth syndrome, Imatinib Mesylate, Female, business, medicine.drug
Abstract

More than 50 individuals with activating variants in the receptor tyrosine kinase PDGFRB have been reported, separated based on clinical features into solitary myofibromas, infantile myofibromatosis, Penttinen syndrome with premature aging and osteopenia, Kosaki overgrowth syndrome, and fusiform aneurysms. Despite their descriptions as distinct clinical entities, review of previous reports demonstrates substantial phenotypic overlap. We present a case series of 12 patients with activating variants in PDGFRB and review of the literature. We describe five patients with PDGFRB activating variants whose clinical features overlap multiple diagnostic entities. Seven additional patients from a large family had variable expressivity and late-onset disease, including adult onset features and two individuals with sudden death. Three patients were treated with imatinib and had robust and rapid response, including the first two reported infants with multicentric myofibromas treated with imatinib monotherapy and one with a recurrent p.Val665Ala (Penttinen) variant. Along with previously reported individuals, our cohort suggests infants and young children had few abnormal features, while older individuals had multiple additional features, several of which appeared to worsen with advancing age. Our analysis supports a diagnostic entity of a spectrum disorders due to activating variants in PDGFRB. Differences in reported phenotypes can be dramatic and correlate with advancing age, genotype, and to mosaicism in some individuals.

Published
2020
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47. Overlapping phenotypes between <scp>SHORT</scp> and Noonan syndromes in patients with <scp> PTPN11 </scp> pathogenic variants

Author

Charles Marques, Yline Capri, Anne Guimier, A. Micheil Innes, Jeanne Amiel, Martine Auclair, Julien Thevenon, David A. Dyment, Gilles Morin, Christel Thauvin-Robinet, Corinne Vigouroux, Emmanuelle Ranza, Michèle Mathieu-Dramard, Alain Verloes, and Laurence Faivre

Subjects
Male, musculoskeletal diseases, 0301 basic medicine, MAPK/ERK pathway, congenital, hereditary, and neonatal diseases and abnormalities, MAP Kinase Signaling System, Protein Tyrosine Phosphatase, Non-Receptor Type 11, 030105 genetics & heredity, Biology, Gene product, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, Metabolic Diseases, Genetics, medicine, Humans, Missense mutation, skin and connective tissue diseases, Protein kinase B, Growth Disorders, Genetics (clinical), Genetic heterogeneity, Noonan Syndrome, Genetic Variation, medicine.disease, PTPN11, Nephrocalcinosis, Phenotype, 030104 developmental biology, SHORT syndrome, Hypercalcemia, Noonan syndrome, Female, Mitogen-Activated Protein Kinases, Signal Transduction
Abstract

Overlapping syndromes such as Noonan, Cardio-Facio-Cutaneous, Noonan syndrome (NS) with multiple lentigines and Costello syndromes are genetically heterogeneous conditions sharing a dysregulation of the RAS/mitogen-activated protein kinase (MAPK) pathway and are known collectively as the RASopathies. PTPN11 was the first disease-causing gene identified in NS and remains the more prevalent. We report seven patients from three families presenting heterozygous missense variants in PTPN11 probably responsible for a disease phenotype distinct from the classical Noonan syndrome. The clinical presentation and common features of these seven cases overlap with the SHORT syndrome. The latter is the consequence of PI3K/AKT signaling deregulation with the predominant disease-causing gene being PIK3R1. Our data suggest that the phenotypic spectrum associated with pathogenic variants of PTPN11 could be wider than previously described, and this could be due to the dual activity of SHP2 (ie, PTPN11 gene product) on the RAS/MAPK and PI3K/AKT signaling.

Published
2020
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50. Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol

Author

Divilly, P, Zaremba, N, Mahmoudi, Z, Soholm, U, Pollard, DJ, Broadley, M, Abbink, EJ, de Galan, B, Pedersen-Bjergaard, U, Renard, E, Evans, M, Speight, J, Brennan, A, McCrimmon, RJ, Mullenborn, M, Heller, S, Seibold, A, Mader, JK, Amiel, SA, Pouwer, F, Choudhary, P, Divilly, P, Zaremba, N, Mahmoudi, Z, Soholm, U, Pollard, DJ, Broadley, M, Abbink, EJ, de Galan, B, Pedersen-Bjergaard, U, Renard, E, Evans, M, Speight, J, Brennan, A, McCrimmon, RJ, Mullenborn, M, Heller, S, Seibold, A, Mader, JK, Amiel, SA, Pouwer, F, and Choudhary, P

Abstract

INTRODUCTION: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. METHODS: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. ETHICS AND DISSEMINATION: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations.

Published
2022

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