Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature

<p>Abstract</p> <p>Background</p> <p>Somatotropinoma, a pituitary adenoma characterised by excessive production of growth hormone (GH), is extremely rare in childhood. A genetic defect is evident in some cases; known genetic changes include: multiple endocrine neoplasia type 1 (MEN1<it>)</it>; Carney complex; McCune-Albright syndrome; and, more recently identified, aryl hydrocarbon receptor-interacting protein (AIP). We describe seven children with somatotropinoma with a special focus on the differences between genetic and sporadic forms.</p> <p>Methods</p> <p>Seven children who presented in our regional network between 1992 and 2008 were included in this retrospective analysis. First-type therapy was somatostatin (SMS) analogues or transsphenoidal surgery. Control was defined as when insulin-like growth factor-1 (IGF-1) levels were within the normal range for the patient's age at 6 months after therapy, associated with decreasing tumour volume.</p> <p>Results</p> <p>Patients were aged 5-17 years and the majority (n = 6) were male. Four patients had an identified genetic mutation (McCune-Albright syndrome: n = 1; MEN1: n = 1; AIP: n = 2); the remaining three cases were sporadic. Accelerated growth rate was reported as the first clinical sign in four patients. Five patients presented with macroadenoma; invasion was noted in four of them (sporadic: n = 1; genetic: n = 3). Six patients were treated with SMS analogues; normalisation of IGF-1 occurred in one patient who had a sporadic intrasellar macroadenoma. Multiple types of therapy were necessary in all patients with an identified genetic mutation (4 types: n = 1; 3 types: n = 2; 2 types: n = 1), whereas two of the three patients with sporadic somatotropinoma required only one type of therapy.</p> <p>Conclusions</p> <p>This is the first series that analyzes the therapeutic response of somatotropinoma in paediatric patients with identified genetic defects. We found that, in children, genetic somatotropinomas are more invasive than sporadic somatotropinomas. Furthermore, SMS analogues appear to be less effective for treating genetic somatotropinoma than sporadic somatotropinoma.</p

1H-NMR-Based Metabolomic Profiling of CSF in Early Amyotrophic Lateral Sclerosis

Background: Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to analyze the CSF of patients with ALS by 1 H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS. Methodology: CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional 1 H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses. Principal Findings: Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites reveale

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Cancer du sein et hormonothérapie : de la conception à la mise en place d'un atelier collectif d'éducation thérapeutique

Hormone-dependant breast cancer affect about 50 000 new women every year. A lot of these women will receive for several years a hormonal therapy in their care pathways to decrease the risk of recurrence of this cancer. This treatment has many adverse side effects which may impair the life quality of patients and reduce their medication adherence. The Bayeux hospital oncology and pharmacy units therefore created an education therapeutic collective workshop for patients who take hormonal therapy for their breast cancer. The aims of this workshop are to increase support for these patients and improve their medication adherence with some entertainments. We developed several tools to make those moments dynamic and playful like “True or False” cards about misconceptions, boards to be completed about drug mechanism of action, and cards about what to do if adverse reactions occur. A patient’s telephone follow-up has been also established afterwards. Overall thirty-nine patients took part in therapeutic education sessions over a period of 1,5 years. We were not able to demonstrate an improvement of medication adherence. But the patient’s overall satisfaction was excellent about these sessions. This encourages us to continue and improve that workshop by developing other sessions about food and physical activity. A development of a practical guide for patients about hormonal therapy would bring real added value to our therapeutic education workshop.Le cancer du sein hormonodépendant touche plus de 50 000 nouvelles femmes chaque année. Ces femmes recevront pour la plupart au cours de leur parcours de soin une hormonothérapie sur plusieurs années afin de diminuer le risque de récidive de ce cancer. Ce traitement a de nombreux effets indésirables pouvant altérer significativement la qualité de vie des patientes, ce qui peut diminuer leur observance au traitement. C’est pourquoi les services d’oncologie et de pharmacie de l’hôpital de Bayeux ont créé un atelier collectif d’éducation thérapeutique des patientes sous hormonothérapie dans le cadre de leur cancer du sein. Cet atelier a pour objectif de renforcer l’accompagnement de ces patientes et leur adhésion à l’hormonothérapie à travers différentes animations. Nous avons créé plusieurs outils afin de rendre ces ateliers dynamiques et ludiques, comme des cartes « Vrai-Faux » sur certaines idées reçues, des planches de fonctionnement du traitement à compléter ou encore des cartes sur les conduites à tenir en cas de survenue d’effets indésirables. Un suivi téléphonique des patientes à distance a également été mis en place. Au total 39 patientes ont participé à cet atelier sur une période de 1,5 ans. Nous n’avons pu démontrer une amélioration de l’observance. Cependant la satisfaction globale des patientes envers l’atelier est excellente. Cela nous encourage à le poursuivre et à l’améliorer en développant d’autres ateliers sur les thèmes de l’alimentation et l’activité physique. De plus la mise en place d’un guide pratique sur l’hormonothérapie pour les patientes apportera une vraie plus-value à l’atelier

Evolution et recours aux soins des enfants atteints de maladie de Crohn et de rectocolite hémorragique en Bretagne (1994-2001)

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Patients’ perceptions on the usability of the SurePal™ self-injection device for Omnitrope: a questionnaire-based observational study conducted in paediatric patients in France

Background: A questionnaire-based survey was conducted to evaluate attitudes towards a reusable self-injection system, SurePal™, among paediatric patients with growth disturbances who were prescribed treatment with somatropin (Omnitrope ® ) as part of routine clinical practice. Methods: This cross-sectional survey was incorporated into the multinational, multi-centre, noninterventional PAtients TReated with Omnitrope ® (PATRO) Children study. Questions were mainly focused on five areas: the attractiveness of SurePal™; training received; use of the device; opinion of the low-drug wastage system; experience compared with previous devices used (among pretreated patients). Results: Final results from participants in France are reported. Completed questionnaires were returned by 409 participants. Most patients (55%) were male and 89% were recombinant human growth hormone (rhGH)-treatment naïve. Around 57% of children completed the questionnaire by themselves, while 43% had help from a family member/other person. The mean (standard deviation) age of all participants was 11.3 (3.6) years, and most patients were aged 10–12 years ( n = 126) or 13–15 years ( n = 117). Overall, 86% of patients reported that preparing SurePal™ for injection was easy/very easy. Similarly, 83% reported that performing injections with SurePal™ was easy/very easy. The attractiveness of SurePal™ was rated as good/excellent by the majority (85%) of patients; this proportion was similarly high (> 80%) across all age groups. The dose-memory function was rated as helpful/very helpful by 54% of patients. Of the 174 patients who reported using the low drug-waste feature, 90% found it to be helpful/very helpful. Among the 24 pretreated patients, 17 reported that SurePal™ was better/much better than their previous device. Conclusions: This questionnaire-based survey conducted in a large cohort of paediatric patients with growth disturbances from France confirms the ease of use of SurePal™ to support daily administration of Omnitrope ® across all age groups. The demonstrated acceptability of the device may help to improve patient adherence to long-term daily treatment with rhGH

Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man

Abstract Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/−; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism

Fetal hypothyroidism induced by maternal anti-TSH receptor blocking antibodies and complicated by polyhydramnios despite the absence of goiter. Treatment by intra-amniotic injections of levothyroxine

Fetal hypothyroidism induced by maternal anti-TSH receptor blocking antibodies and complicated by polyhydramnios despite the absence of goiter. Treatment by intra-amniotic injections of levothyroxin

Risk factors and outcomes for patients with follicular lymphoma who had histologic transformation after response to first-line immunochemotherapy in the PRIMA trial

Purpose: To study the outcome of histologic transformation (HT) in a large prospective cohort of patients with follicular lymphoma (FL) who previously responded to immunochemotherapy. Patients and Methods: After a median 6-year follow-up of 1,018 randomly assigned patients from the PRIMA trial, disease progression was observed in 463 patients, 194 of whom had histologic documentation. Results: Forty patients had histology consistent with HT, and 154 had untransformed FL (median time to recurrence, 9.6 v 22.8 months, respectively; P = .018). Thirty-seven percent of biopsies performed during the first year of follow-up showed HT corresponding to 58% of all HTs. Altered performance status, anemia, high lactate dehydrogenase level, "B" symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis were identified as HT risk factors. Response (complete v partial) to immunochemotherapy or rituximabmaintenance had no impact on the risk of HT. After salvage treatment, patients with HT had less frequent complete response (50.3% v 67.4%; P = .03) and more disease progression (28.2% v 9.6%; P < .001) than patients without HT. Estimated overall survival for the patientswith HTwas poorer (median, 3.8 v 6.4 years; hazard ratio, 3.9; 95% CI, 2.2 to 6.9). Autologous stem cell transplantation improved the outcomes of patientswith HT (median overall survival, not reached v 1.7 years) but not of patients with persistent FL histology. Conclusion: HT in patients with FL who previously responded to immunochemotherapy is an early event associated with a poor outcome that may deserve intensive salvage with autologous stem cell transplantation. These data emphasize the necessity for biopsy at the first recurrence of FL