Evaluation of auditory pathway excitability using a pre-operative trans-tympanic electrically evoked auditory brainstem response under local anesthesia in cochlear implant candidates.

OBJECTIVE: Subjective promontory stimulation is used to evaluate cochlear implant (CI) candidacy, but the test reliability is low. Electrically evoked auditory brainstem response (EABR) can verify the function of the auditory system objectively. This study's procedure uses a trans-tympanic rounded bent-tip electrode to perform pre-operative EABR under local anaesthesia (LA-TT-EABR) using MED-EL Software and Hardware. This study aimed to determine usability and effectiveness for CI candidates. DESIGN: We hypothesised that LA-TT-EABR waveforms of good quality would be related to successful hearing outcomes. We assumed that the duration of hearing loss/deafness was a confounding factor to study outcomes. STUDY SAMPLE: 19 borderline CI candidates. RESULTS: Positive LA-TT-EABR results were confirmed in 14 patients. LA-TT-EABR's mean latency was 2.05 ± 0.31 ms (eII/eIII) and 4.24 ± 0.39 ms (eIV/eV). Latencies weren't statistically different from intra-operative EABR elicited by basal CI contacts. All positive LA-TT-EABR patients benefitted from CI and speech performance improved one year after implantation. One patient with negative LA-TT-EABR was cochlear-implanted and had no hearing sensation. CONCLUSIONS: LA-TT-EABR is a tool in the frame of pre-operative objective testing the auditory pathway. It seems useful for clinical testing CI candidacy. Based on this study's outcomes, LA-TT-EABR should be recommended for uncertain CI candidates.

Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy-dependent modification of the keratinocyte immunophenotype.

BACKGROUND: Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of T helper (Th)1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced our understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict the importance of a specific pathway in AD or cellular responses to different inflammatory stimuli. OBJECTIVES: To understand changes in keratinocyte transcriptomic programmes in human cutaneous disease during development of inflammation and in response to treatment. METHODS: We performed in silico deconvolution of the whole-skin transcriptome. Using co-expression clustering and machine-learning tools, we resolved the gene expression of bulk skin (seven datasets, n = 406 samples), firstly, into keratinocyte phenotypes identified by unsupervised clustering and, secondly, into 19 cutaneous cell signatures of purified populations from publicly available datasets. RESULTS: We identify three unique transcriptomic programmes in keratinocytes - KC1, KC2 and KC17 - characteristic of immune signalling from disease-associated Th cells. We cross-validate those signatures across different skin inflammatory conditions and disease stages and demonstrate that the keratinocyte response during treatment is therapy dependent. Broad-spectrum treatment with ciclosporin ameliorated the KC17 response in AD lesions to a nonlesional immunophenotype, without altering KC2. Conversely, the specific anti-Th2 therapy, dupilumab, reversed the KC2 immunophenotype. CONCLUSIONS: Our analysis of transcriptomic signatures in cutaneous disease biopsies reveals the effect of keratinocyte programming in skin inflammation and suggests that the perturbation of a single axis of immune signal alone may be insufficient to resolve keratinocyte immunophenotype abnormalities.

Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta-analysis.

OBJECTIVE: To establish, based on a systematic literature review, the frequency of pathogenic submicroscopic chromosomal aberrations in fetuses that are not at increased risk for unbalanced structural chromosomal aberrations, with the aim of determining whether high-resolution testing for submicroscopic aberrations is beneficial in a general pregnant population. METHODS: EMBASE, PubMed, Web of Science and CENTRAL databases were searched systematically on 3 June 2016 for all relevant articles on the prevalence of pathogenic submicroscopic copy number variants (CNVs) in fetuses referred for prenatal invasive testing because of advanced maternal age (AMA) or parental anxiety (ANX). Relevant full-text articles were analyzed and the prevalence of submicroscopic CNVs was calculated based on the extracted data. Meta-analysis was conducted in a pooled cohort of 10 614 fetuses based on the 10 largest studies (n > 300) of a total of 19 that were relevant. RESULTS: Pooled estimate analysis indicated that 0.84% (95% CI, 0.55-1.30%) of fetuses that had invasive testing because of AMA/ANX carried a pathogenic clinically significant submicroscopic aberration. The onset/penetrance of submicroscopic findings was studied in 10 314 fetuses reported in eight papers that presented aberrant cases with all necessary details to allow assessment of the findings. The pooled estimates resulting from meta-analysis of the data indicated that an early-onset syndromic disorder was detected in 0.37% (95% CI, 0.27-0.52%) of cases, a susceptibility CNV was found in 0.30% (95% CI, 0.14-0.67%) and late-onset diseases were reported in 0.11% (95% CI, 0.05%-0.21%). The prevalence of early-onset syndromic disorders caused by a submicroscopic aberration was calculated to be 1:270. When the risk for submicroscopic aberrations is added to the individual risk for microscopic chromosomal aberrations, all pregnant women have a risk of higher than 1 in 180 for a relevant chromosomal aberration, and pregnant women under 36 years of age have a higher risk for submicroscopic pathogenic aberrations than for Down syndrome. CONCLUSION: This systematic review shows that a significant proportion of fetuses in a general pregnant population carry a submicroscopic pathogenic CNV. Based on these figures, all women should be informed on their individual risk for all pathogenic chromosomal aberrations and not only for common trisomies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Choosing between Higher and Lower Resolution Microarrays: do Pregnant Women Have Sufficient Knowledge to Make Informed Choices Consistent with their Attitude?

Developments in prenatal testing allow the detection of more findings. SNP arrays in prenatal diagnosis (PND) can be analyzed at 0.5 Mb resolution detecting more clinically relevant anomalies, or at 5 Mb resolution. We investigated whether women had sufficient knowledge to make informed choices regarding the scope of their prenatal test that were consistent with their attitude. Pregnant women could choose between testing at 5 or at 0.5 Mb array. Consenting women (N = 69) received pre-test genetic counseling by phone and filled out the Measure of Informed Choice questionnaire designed for this study. Choices based on sufficient knowledge and consistent with attitude were considered informed. Sixty-two percent of the women made an adequately informed choice, based on sufficient knowledge and attitude-consistent with their choice of microarray resolution. Women who made an informed choice, opted for 0.5 Mb array resolution more often. There were no differences between women making adequately informed or less informed choices regarding level of experienced anxiety or doubts. Over time on T0 and T1, anxiety and doubts significantly decreased. While previous studies demonstrated that knowledge is an important component in informed decision-making, this study underlines that a consistent attitude might be equally important for decision-making. We advocate more focus on attitude-consistency and deliberation as compared to only a strong focus on knowledge.

Nano-size scaling of alloy intra-particle vs. inter-particle separation transitions: prediction of distinctly interface-affected critical behaviour.

Phase-separation second-order transitions in binary alloy particles consisting of ∼1000 up to ∼70 000 atoms (∼1-10 nm) are modeled focusing on the unexplored issue of finite-size scaling in such systems, particularly on evaluation of correlation-length critical exponents. Our statistical-thermodynamic approach is based on mean-field analytical expression for the Ising model free energy that facilitates highly efficient computations furnishing comprehensive data for fcc rectangular nanoparticles (NPs). These are summed up in intra- and inter-particle scaling plots as well as in nanophase separation diagrams. Temperature-induced variations in the interface thickness in Janus-type intra-particle configurations and NP size-dependent shifts in the critical temperature of their transition to solid-solution reflect power-law behavior with the same critical exponent, ν = 0.83. It is attributed to dominant interfacial effects that are absent in inter-particle transitions. Variations in ν with nano-size, as revealed by a refined analysis, are linearly extrapolated in order to bridge the gap to larger particles within and well beyond the nanoscale, ultimately yielding ν = 1.0. Besides these findings, the study indicates the key role of the surface-area to volume ratio as an effective linear size, revealing a universal, particle-shape independent, nanoscaling of the critical-temperature shifts.

Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484).

Meta-analyses, published in 2008-2010, have confirmed abnormally low serum brain-derived neurotrophic factor (BDNF) concentrations in depressed patients and normalization of this by antidepressant treatment. These findings are believed to reflect peripheral manifestations of the neurotrophin hypothesis, which states that depression is secondary to an altered expression of BDNF in the brain. Since the publication of these meta-analyses, the field has seen a huge increase in studies on these topics. This motivated us to update the evidence on the aforementioned associations and, in addition, to compile the data on serum BDNF concentrations in relation to the symptom severity of depression. Using a manifold of data as compared with earlier meta-analyses, we find low serum BDNF concentrations in 2384 antidepressant-free depressed patients relative to 2982 healthy controls and to 1249 antidepressant-treated depressed patients (Cohen's d=-0.71 and -0.56, P-values <0.0000001). When publication bias is accounted for, these effect-sizes become substantially smaller (d=-0.47 and -0.34, respectively, P-values<0.0001). We detect between-study heterogeneity in outcomes for which only year of publication and sample size are significant moderators, with more recent papers and larger samples sizes in general being associated with smaller between-group differences. Finally, the aggregated data negate consistent associations between serum BDNF concentrations and the symptom severity of depression. Our findings corroborate the claim that altered serum BDNF concentrations are peripheral manifestations of depression. However, here we highlight that the evidence for this claim is slimmer as was initially thought and amidst a lot of noise.

Sequence variation in virulence-related genes of Bordetella pertussis isolates from Poland in the period 1959-2013.

This study aimed to characterise Bordetella pertussis isolates circulating in Poland since 1959. Sequence analysis of ptxA, ptxC, prn, tcfA, fim2, fim3 and ptxP for 175 clinical isolates and currently and previously used vaccine strains was performed. Clinical isolates from the period 1995-2013 were found to be different to three currently used vaccine strains harbouring the allelic combination ptxA2-ptxC1-ptxP1-prn1-tcfA2-fim2-1-fim3-1, seen frequently in Poland in the early pertussis vaccination period but not found after 1995. Generally, among B. pertussis isolates from the period 2000-2013, two genotypes predominated, ptxA1-ptxC1-ptxP1-prn1-tcfA2-fim2-2-fim3-1 and ptxA1-ptxC1-ptxP1-prn2-tcfA2-fim2-1-fim3-1, with frequencies of 45% and 32.5%, respectively. The isolates harbouring ptxA1-ptxC2-ptxP3-prn2-tcfA2-fim2-1-fim3-2 and ptxA1-ptxC2-ptxP3-prn2-tcfA2-fim2-1-fim3-1 profiles, currently highly prevalent within other European Union (EU) countries, were rarely found in Poland, as they circulated in the period 2000-2013 with frequencies of 10% and 5%, respectively. We hypothesise that several previous changes of strain composition in whole-cell pertussis vaccine produced locally and used since 1960 in Poland resulted in a more diverse immune pressure in the population, resulting in different prevalence of alleles compared to elsewhere.

Cross-priming amplification for detection of bovine viral diarrhoea virus species 1 and 2.

AIMS: The aim of the study was the development of cross-priming amplification for ubiquitous detection of bovine viral diarrhoea virus (BVDV) species 1 and 2. METHODS AND RESULTS: Three and five specific primers, respectively, for the detection of BVDV-1 and BVDV-2, were designed on the basis of the sequences of the 5'UTR region. Incubation temperature and reaction time were determined. The optimal incubation conditions using water bath were 63°C for 75 min. Reverse transcription step (RT) was not required. The results were visualized under UV-light as a bright yellow fluorescence in positive samples. Additional method for results interpretation was agarose gel electrophoresis. Positive samples showed the presence of ladder-like banding patterns, formed by harpin-like cross-priming amplification (CPA) products. Sensitivity of CPA was compared with conventional RT-PCR and real-time RT-PCR. The CPA detection limit was 3500 copies for BVDV-1 and 80000 copies for BVDV-2 per reaction. For RT-PCR it was 350 and 80 copies for BVDV-1 and BVDV-2, respectively, and for real-time RT-PCR it was 35 copies for BVDV-1 and 80 copies for BVDV-2. The sensitivity of the developed method is sufficient to detect persistently infected (PI) animals. Positive results were found in 24 of 25 BVDV isolates belonging to species 1 and 2. Additionally, one false-negative result for BVDV-2 was detected. There were no false-positive results in negative samples and in the negative control. Both sets of primers used for the detection of BVDV-1 and BVDV-2 were not able to detect atypical pestiviruses. CPA positive results were confirmed by RT-PCR and real-time RT-PCR. CONCLUSIONS: CPA is a rapid method for the detection of BVDV-1 and BVDV-2 in field samples from PI animals. SIGNIFICANCE AND IMPACT OF STUDY: This is the first report on the application of the CPA method for the detection of BVDV.

Evaluating the post-copulatory sexual selection hypothesis for genital evolution reveals evidence for pleiotropic harm exerted by the male genital spines of Drosophila ananassae.

The contemporary explanation for the rapid evolutionary diversification of animal genitalia is that such traits evolve by post-copulatory sexual selection. Here, we test the hypothesis that the male genital spines of Drosophila ananassae play an adaptive role in post-copulatory sexual selection. Whereas previous work on two Drosophila species shows that these spines function in precopulatory sexual selection to initiate genital coupling and promote male competitive copulation success, further research is needed to evaluate the potential for Drosophila genital spines to have a post-copulatory function. Using a precision micron-scale laser surgery technique, we test the effect of spine length reduction on copulation duration, male competitive fertilization success, female fecundity and female remating behaviour. We find no evidence that male genital spines in this species have a post-copulatory adaptive function. Instead, females mated to males with surgically reduced/blunted genital spines exhibited comparatively greater short-term fecundity relative to those mated by control males, indicating that the natural (i.e. unaltered) form of the trait may be harmful to females. In the absence of an effect of genital spine reduction on measured components of post-copulatory fitness, the harm seems to be a pleiotropic side effect rather than adaptive. Results are discussed in the context of sexual conflict mediating the evolution of male genital spines in this species and likely other Drosophila.

Presence of the HLA-A*3101 allele in a familial case of drug reaction with eosinophilia and systemic symptoms, secondary to carbamazepine.

Anticonvulsants such as carbamazepine and phenytoin are associated with adverse skin reactions ranging from maculopapular exanthems to more severe reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome and toxic epidermal necrolysis. In addition to their antiepileptic role, anticonvulsants are also used to treat pain syndromes including trigeminal neuralgia. Until recently, the associated skin reactions were thought to be unpredictable; however, the current literature suggests a genetic predisposition involving the human leucocyte antigen (HLA) in cutaneous reactions associated with carbamazepine usage. We present two familial cases of DRESS secondary to carbamazepine, in which an underlying genetic predisposition and allelic association were identified.

Small-molecule inhibitors of the cystic fibrosis transmembrane conductance regulator increase pancreatic endocrine cell development in rat and mouse.

AIMS/HYPOTHESIS: The main objective of this work was to discover new drugs that can activate the differentiation of multipotent pancreatic progenitors into endocrine cells. METHODS: In vitro experiments were performed using fetal pancreatic explants from rats and mice. In this assay, we examined the actions on pancreatic cell development of glibenclamide, a sulfonylurea derivative, and glycine hydrazide (GlyH-101), a small-molecule inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR). We next tested the actions of GlyH-101 on in vivo pancreatic cell development. RESULTS: Glibenclamide (10 nmol/l-100 µmol/l) did not alter the morphology or growth of the developing pancreas and exerted no deleterious effects on exocrine cell development in the pancreas. Unexpectedly, glibenclamide at its highest concentration promoted endocrine differentiation. This glibenclamide-induced promotion of the endocrine pathway could not be reproduced when other sulfonylureas were used, suggesting that glibenclamide had an off-target action. This high concentration of glibenclamide had previously been reported to inhibit CFTR. We found that the effects of glibenclamide on the developing pancreas could be mimicked both in vitro and in vivo by GlyH-101. CONCLUSIONS/INTERPRETATION: Collectively, we demonstrate that two small-molecule inhibitors of the CFTR, glibenclamide and GlyH-101, increase the number of pancreatic endocrine cells by increasing the size of the pool of neurogenin 3-positive endocrine progenitors in the developing pancreas.

In vitro diagnostic assays are effective during the acute phase of delayed-type drug hypersensitivity reactions.

BACKGROUND: Previous reports have suggested that drug-specific lymphocyte proliferation assays (LPA) can be used retrospectively to confirm the culprit drug following delayed-type drug hypersensitivity reactions (DHR). However, only limited evidence supports their use in aiding acute clinical management. The aim of this study was to compare the LPA against combination cytokine assays for potential use in the acute setting. METHODS: A total of 43 patients with DHR (19 during the acute reaction, 20 after recovery, four during acute and after recovery) and 14 control subjects without DHR were investigated using ex vivo analysis of drug-specific proliferation, and interferon (IFN)-γ and interleukin (IL)-4 production. RESULTS: Healthy controls showed negative drug-specific proliferation and cytokine release in contrast to individuals with a known sensitivity (P < 0·0001). The assays demonstrated a test specificity of 95% (LPA), 83% (IFN-γ) and 92% (IL-4). The sensitivity of combined measurement of drug-specific IFN-γ and IL-4 cytokines during acute DHR was better than LPA (82% vs. 50%), but all assays were less sensitive during the recovery phase. The correlation between LPA and IFN-γ assays was strong (r = 0·7, P < 0·0001), whereas the IL-4 assay did not correlate as well with either of these assays. In contrast to LPA, drug enzyme-linked immunosorbent spot assays showed positive responses in patients concurrently taking immunosuppressive medication. CONCLUSIONS: In vitro assays of drug-specific IFN-γ and IL-4 production offer potential for use as rapid diagnostic tests. Cytokine detection offers distinct advantages over the LPA, including a shorter assay time, a greater sensitivity and effectiveness in testing immunosuppressed patients.

Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.

Diabetes mellitus (DM) is one of the most common chronic disorders of children and adults. Several reports have suggested an increased incidence of maternal transmission in some forms of DM. Therefore, we tested a pedigree with maternally transmitted DM and deafness for mitochondrial DNA mutations and discovered a 10.4 kilobase (kb) mtDNA deletion. This deletion is unique because it is maternally inherited, removes the light strand origin (OL) of mtDNA replication, inhibits mitochondrial protein synthesis, and is not associated with the hallmarks of mtDNA deletion syndromes. This discovery demonstrates that DM can be caused by mtDNA mutations and suggests that some of the heterogeneity of this disease results from the novel features of mtDNA genetics.

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.

[Chronic abdominal pain with a rare cause]. / Chronické bolesti bricha s raritní prícinou.

The authors use a case report of a female patient with chronic abdominal pain progressing postprandially as an example to demonstrate the complexity of the diagnostic process in patients with these complaints, as well as a surprising peroperative finding in which a small neuroendocrine tumour of the small intestine was the cause of the difficulties. The ensuing discussion also deals with other possible causes of chronic abdominal pain associated with eating disorders.

Developmental instability as phenodeviance in a secondary sexual trait increases sharply with thermal stress.

We test for effects of thermal stress applied to pupal flies from Noumea (New Caledonia) and Taipei (Taiwan) on developmental instability (DI) in the male sex comb of Drosophila bipectinata, as well as on pre-adult survivorship and adult body size. The temperature treatments were Low (25 °C), High (29 °C) and Variable (18 h at 29 °C, 6 h at 34 °C). Although the Variable treatment reduced survivorship and body size, absolute comb size and fluctuating asymmetry generally were invariant across treatments. In contrast, comb phenodeviance increased with stress in both populations. Phenodeviance in one comb segment (C2) increased sharply with stress, whereas phenodeviance in a second major segment (C1) also increased with stress but only in Noumea flies. A major conclusion is that phenodeviations induced in a secondary sexual trait reflect the developmental environment that also damages fitness components, a foundation stone of the hypothesis that expressions of DI reveal phenotypic quality in sexual selection.

Bovine neonatal pancytopenia in calves in Poland.

Bovine neonatal pancytopenia (BNP), a newly emerged syndrome of discussed etiology in calves, has been diagnosed since 2006. Here we describe first cases of BNP in Poland. Between September 2008 and April 2011, 62 cases of BNP were diagnosed in dairy calves. Bleeding skin lesions were mostly pronounced in summer and early autumn. Severe thrombocytopenia was observed in all sick animals. All calves came from herds vaccinated against BVDV infection with PregSure BVD vaccine (Pfizer). Substitution of colostrum from dams of BNP positive calves with colostrum from dams from herds free of BNP was the only effective measure to avoid new cases in affected herds.

[Vascular reconstructions infections in the aortofemoral region]. / Infekce cévních rekonstrukcí v aortofemorální oblasti.

INTRODUCTION: The incidence of prosthetic vascular graft infections in the aortofemoral region is reported at 0.6-3%. These complications are burdened with a high mortality of up to 50% and an amputation rate of up to 20%. The aim of our study was to give a complex view on the diagnostic and treatment possibilities of these serious complications of reconstructive vascular surgery. MATERIAL AND METHODS: Prosthetic bypass grafts were performed in 1088 patients in the aortofemoral region between 2001-2011 at the Department of Surgery, Teaching Hospital and the Faculty of Medicine, Charles University, in Pilsen. 24 (2.2%) patients suffered from graft infection at various time intervals after primary vascular reconstruction. Clinical examination, computed tomography and positron emission tomography were the main diagnostic methods of vascular graft infection. "In situ" reconstructions dominated over extra-anatomic reconstructions. When the infection involved only the peripheral part of the prosthetic graft, a more conservative approach - local debridement and drainage - was used. RESULTS: The mortality of the patients was 20.8%, high amputation rate 12.5%, and morbidity rate 58.3%, respectively. The average time of hospitalization in surviving patients was 46.5 days. Primary 30-day patency rate in "in situ" and extra-anatomic reconstructions was 100 and 60%, respectively. CONCLUSION: Prosthetic vascular graft infections in the aortofemoral region require tailored multidisciplinary treatment approach in vascular centres. "In situ" reconstructions are the method of first choice. A more conservative approach in infections involving only the peripheral part of the vascular reconstruction has a positive treatment effect.

Adherence and quality of life in children receiving rhGH treatment.

Short stature may have a major impact on quality of life (QoL), not only during adulthood but also during childhood. Treatment by growth hormone may induce improvement in QoL through height gain, as shown in recent articles, with an increase in general health-related and also height-specific QoL assessed by self-reports and parental reports. In a paper published by our team, we show altered general-health QoL in patients with very short stature (≤ -3 SD) and an improvement in general and height-specific scales in the complete population (≤ -2 SD) after one year of recombinant human growth hormone (rhGH) treatment, perceived both by children and their parents, with a moderate positive correlation with height gain. Adequate results in terms of height gain depend on different factors: the patient's age, underlying condition for which rhGH is prescribed and dose of rhGH treatment, among others. Daily injections may cause a significant burden for the child and family, and may alter adequate adherence to treatment. Identifying positive and negative factors in the patient and in the healthcare providers-patient team and encouraging a shared decision-making process are important for improving the patient's adherence to treatment. New long-acting forms of rhGH that will be available in the next few years may play an important part in improving treatment-related QoL and adherence to treatment. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.