Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.

BACKGROUND: This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. METHODS AND RESULTS: Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. CONCLUSIONS: Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Thyroid Hormone Resistance: Multicentrical Case Series Study.

Resistance to thyroid hormone syndrome (RTHS) is defined as increased thyroxine and triiodothyronine associated with normal or increased thyrotropin. This is usually due to a pathogenic variant of the gene coding for thyroid hormone receptor B (THRB). THRB is a rare genetic disorder characterized by an altered response of target tissue to the thyroid hormone action. Retrospective cross-sectional observational study with diagnosis of RTHS evaluated in secondary and tertiary hospitals for 6 years, from 2014 to 2020, in order to describe variables including age, sex, anthropometric data, clinical and biochemical characteristics of patients, who were divided according to age, in a pediatric group from 0 to 14 years (index cases), and an adult group composed of adult relatives of index cases. A molecular analysis of the THRB gene was performed. The total retrospective cohort included 7 pediatric patients and 15 adults. We found 22 cases with a clear male predominance (14/22). Mean age is 24.8 years old (22 days-70 years). Patients were referred because of symptoms 18.2% (4/22), analysis results 22.7% (5/22), or familial study 59.1% (13/22). About 31.8% (7/22) cases show goiter, 31.8% (7/22) sympathetic symptoms and 13.6% (3/22) abnormalities in behavior. In most cases, 77.3%, (17/22) show familial background of thyroid abnormalities. It is important to remark that 18.2% (4/22) relatives received previous incorrect treatments such as thyroidectomy, because of wrong diagnosis. In conclusion, a better understanding of RTHS, its prompt molecular diagnosis and genetic counseling, could avoid unnecessary tests and inappropriate treatments.

Diagnostic Accuracy of the Panbio Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Rapid Test Compared with Reverse-Transcriptase Polymerase Chain Reaction Testing of Nasopharyngeal Samples in the Pediatric Population.

We conducted a multicenter clinical validity study of the Panbio coronavirus disease 2019 Antigen Rapid Test of nasopharyngeal samples in pediatric patients with coronavirus disease 2019-compatible symptoms of ≤5 days of evolution. Our study showed limited accuracy in nasopharyngeal antigen testing: overall sensitivity was 45.4%, and 99.8% of specificity, positive-predictive value was 92.5%.

Increased Severity of Mycoplasma pneumoniae Infections in Spanish Children.

BACKGROUND: Since the end of 2023, an elevated incidence and severity of Mycoplasma pneumoniae infections among children in Asia has been noted. Subsequently, this trend was observed in several European countries although limited data are currently available. We conducted a national study to delineate the ongoing M. pneumoniae outbreak in our country. METHODS: A multicenter retrospective observational study was conducted across 32 hospitals in Spain, encompassing patients under 18 years old hospitalized for M. pneumoniae infection from January 2023 to March 2024. Infection was confirmed by positive polymerase chain reaction and/or by 2 serological tests. RESULTS: A total of 623 children were included, with 79% of cases diagnosed in the final 3 months of the study period. Pneumonia was the most common diagnosis (87%). Respiratory symptoms were present in 97% of cases, with 62% requiring oxygen supplementation and 14% requiring admission to the pediatric intensive care unit (PICU). Risk factors for PICU admission included the presence of neurological symptoms, hypoxemia and a history of prematurity. Children admitted to the PICU exhibited significantly higher neutrophil counts upon admission. CONCLUSIONS: We have observed a notable increase in hospital admissions, including PICU support by up to 14%, due to M. pneumoniae infection in our country since November 2023, indicative of a more severe clinical course associated with this pathogen.

Factors associated with knowledge and vaccination intention for human papillomavirus on trans girls by their main caregiver: A cross-sectional study.

Introduction: Trans women are highly affected by the human papillomavirus (HPV) and are at risk of suffering from HPV-related diseases such as oropharyngeal, anal, penile, or neovaginal neoplasia. HPV vaccination seems to be a good strategy to reduce HPV-related diseases, mainly during the early age before the first sexual intercourse, but only cisgender girls are covered by the National Health Services, while some high-risk groups such as trans girls are not included. Achieving a high vaccination rate is important in the adolescent population, but there are many factors that could affect it, such as lack of knowledge about HPV or fear of side effects by patients and main caregivers. The aim of our study is to analyze the knowledge of trans girls' main caregivers about HPV-related diseases in the general population and, in particular, in trans women, as well as factors associated with HPV vaccination intention. Methods: A cross-sectional study was performed with the collaboration of main caregivers of adolescent trans girls, between 9 and 16 years old, assisted in two reference centers' multidisciplinary Gender Diversity Units. Information was requested through a self-completed questionnaire: HPV-related diseases Knowledge Transwomen questionnaire (HPV-TQ) was elaborated based on a 19-item self-administered questionnaire and score was standardized from 0 to 19 points. Percentage of correct answers was calculated and defined by the group of high scores that showed over 70% correct answers. Results: A total of 65 main caregivers were included. Almost all main caregivers were mothers with a Caucasian ethnicity. The HPV-TQ average score was 11 (3.7) with an average correct answer of 58.1% (19.6). Only 17/65 (26.1%) of main caregivers were highly knowledgeable in HPV. Of 65 trans girls, 14 were already vaccinated (29.8% of trans girls over 12 years old); 78.5% were not vaccinated and only 21.5% had intentions to be vaccinated. The group with a high score in HPV-TQ had a longer follow-up at the transgender unit, a higher maternal vaccination rate, and a positive family history of HPV-related disease, especially in mothers. Conclusion: Adolescent trans girls attended to in our units had a low rate and a low intention of vaccination against HPV. Education on and promotion and prevention of transgender HPV-related diseases should probably be implemented to achieve a higher knowledge and vaccination coverage in adolescent trans girls.

Nirsevimab for the prevention of respiratory syncytial virus disease in children. Statement of the Spanish Society of Paediatric Infectious Disease (SEIP).

INTRODUCTION: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. OBJECTIVES: To provide recommendations for the administration of nirsevimab for prevention of RSV disease. METHODS: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions. RESULTS: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis. CONCLUSIONS: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.

Adequacy of the 10 mg/kg Daily Dose of Antituberculosis Drug Isoniazid in Infants under 6 Months of Age.

In 2010, the WHO recommended an increase in the daily doses of first-line anti-tuberculosis medicines in children. We aim to characterize the pharmacokinetics of the once-daily isoniazid (INH) dose at 10 mg/kg of body weight in infants <6 months of age. We performed a multicenter pharmacokinetic study in Spain. The N-acetyltransferase 2 gene was analyzed to determine the acetylation status. Samples were analyzed using a validated UPLC-UV assay. A non-compartmental pharmacokinetic analysis was performed. Twenty-three pharmacokinetic profiles were performed in 20 infants (8 females) at a median (IQR) age of 19.0 (12.6-23.3) weeks. The acetylator statuses were homozygous fast (n = 1), heterozygous intermediate (n = 12), and homozygous slow (n = 7). INH median (IQR) Cmax and AUC0-24h values were 4.8 (3.7-6.7) mg/L and 23.5 (13.4-36.7) h*mg/L and the adult targets (>3 mg/L and 11.6-26.3 h*mg/L) were not reached in three and five cases, respectively. The age at assessment or acetylator status had no impact on Cmax values, but a larger INH AUC0-24h (p = 0.025) and trends towards a longer half-life (p = 0.055) and slower clearance (p = 0.070) were observed in homozygous slow acetylators. Treatment was well tolerated; mildly elevated alanine aminotransferase levels were observed in three cases. In our series of young infants receiving isoniazid, no major safety concerns were raised, and the target adult levels were reached in most patients.

Optimization of the molecular diagnosis of the acute hepatitis E virus infection.

To evaluate the diagnostic value of the combination of two broad-range PCR assays targeting two different and conserved regions of the viral genome for the diagnosis of acute Hepatitis E virus (HEV) infection. Patients with acute hepatitis were prospectively recruited. In all, HEV-IgM antibodies were tested together with evaluation of HEV viraemia by two PCR assays (ORF3 and ORF1). The number of individuals exhibiting negative IgM antibody results but carrying viral RNA was calculated by each PCR assay. Four-hundred and seventy individuals were included, of whom 145 (30.8%) were diagnosed as having acute HEV. Of them, 122 (84.1%) exhibited HEV-IgM antibodies, and 81 (55.8%) had detectable viral RNA for at least one PCR. Using the ORF3 molecular assay, 70 (48.3%) individuals were identified with HEV infection. When the ORF1 molecular assay was applied, 49 (33.8%) individuals were identified. The ORF3 assay detected viral RNA in 32 patients not detected by the ORF1 assay. In contrast, the ORF1 assay could amplify viral RNA in 11 patients who were not detected by the ORF3 assay. The parallel use of two broad-range PCR assays significantly increased the performance of the molecular diagnosis of HEV.

Temporal changes in the genotypes of Paslahepevirus balayani in southern Spain and their possible link with changes in pig trade imports.

Introduction: Paslahepevirus balayani (HEV) is an endemic zoonotic disease ranked as a major cause of acute hepatitis in Europe. Most infections occurring in Europe are due to the endemic several subtypes of genotype 3, through the consumption of raw or undercooked pork, observing a genotype geographical distribution pattern among countries Because of global changes in the pig and pork trading markets, subtype distribution might vary. We aimed to evaluate the temporal distribution of HEV genotypes in patients from southern Spain with acute hepatitis to determine whether these changes were related to the pig import trade during the study period between 2018 and 2022. Methods: Prospective longitudinal study including patients with acute hepatitis from southern Spain between 2018 and 2022. HEV RNA and antibodies was tested in all patients. In patients with detectable HEV RNA, genotype was obtained. To determine the number of imported pigs and their origins, we checked the official data from the Spanish statistics on international trade of Spanish Minister of Industry during by country of origin during the same study period. Results: A total of 659 patients with acute hepatitis were included in the study. Among them, 162 (24.5%) had at least one marker (IgM or RNA) of acute HEV infection. Among the 71 patients with detectable viral RNA, genotypes could be obtained for 58 (81.6%). The most prevalent HEV genotype was 3f (n = 48; 78.6%), showing a decreasing prevalence of over time, from 100% in 2018 to 70.6% in 2022. Since 2021, the emergence of other genotypes has been determined. A significant increase in the number of animals imported was observed since the beginning of the study. Denmark experienced a significant rise, from 0.03% in 2018 of total imports to 10.4% in 2022. Conclusions: HEV molecular diversity is changing in Spain, could be linked to changes in fattening pig import origin.

Impact on variables of severe hypoglycaemia and healthcare costs of the use of the FreeStyle system in paediatric population with type 1 diabetes mellitus.

INTRODUCTION: Analysis of the impact on severe hypoglycaemia and direct costs of the introduction of the FreeStyle Libre sensor in paediatric population with type 1 Diabetes Mellitus. MATERIAL AND METHODS: Ambispective single-centre study to assess the impact on severe hypoglycaemia and direct costs, focusing on consumption of materials, in paediatric population with type 1 Diabetes Mellitus before and after introduction of the FreeStyle Libre 1 sensor. RESULTS: A significant decrease was found in episodes of severe hypoglycaemia, with 4.2 episodes of severe hypoglycaemia per 100 patients under follow-up versus 0.25 episodes per 100 patients a year after introduction of the system. This represents a cost difference for severe hypoglycaemia, estimated at €6559.52 before introduction and €409.97 after introduction of the FreeStyle Libre sensor. We found a decrease in the daily consumption of capillary blood glucose strips, which translates as a decrease in the cost of materials and helps mitigate the cost of the sensor. The cost in materials for the patient with FreeStyle Libre was €185.13 per patient and year higher than conventional control with capillary blood glucose strips.

Pediatric Chagas disease in the non-endemic area of Madrid: A fifteen-year review (2004-2018).

BACKGROUND: Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004-2018 period, as well as the safety and efficacy of CD treatment on this population. METHODOLOGY/PRINCIPAL FINDINGS: A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p<0.001). Loss to follow- up occurred in 35.3% of patients. CONCLUSIONS/SIGNIFICANCES: Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern.

Metabolic Control of the FreeStyle Libre System in the Pediatric Population with Type 1 Diabetes Dependent on Sensor Adherence.

AIMS: To evaluate the relationship between daily sensor scan rates and changes in HbA1c and hypoglycemia in children. METHODS: We enrolled 145 paediatric T1D patients into a prospective, interventional study of the impact of the FreeStyle Libre 1 system on measures of glycemic control. RESULTS: HbA1c was higher at lower scan rates, and decreased as the scan rate increased to 15-20 scans, after which it rose at higher scan rates. An analysis of the change in hypoglycemia, based on the number of daily sensor scans, showed there was a significant correlation between daily scan rates and hypoglycemia. Subjects with higher daily scan rates reduced all levels of hypoglycaemia. CONCLUSIONS: HbA1c is higher at lower scan rates, and decreases as scan rate increases. Reductions in hypoglycemia were evident in subjects with higher daily scan rates.

Oral saliva swab reverse transcription PCR for Covid-19 in the paediatric population.

OBJECTIVES: To evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR) compared with RT-PCR and antigen rapid diagnostic test (Ag-RDT) on nasopharyngeal swabs (NPS) for SARS-CoV-2 in children. DESIGN: Cross-sectional multicentre diagnostic study. SETTING: Study nested in a prospective, observational cohort (EPICO-AEP) performed between February and March 2021 including 10 hospitals in Spain. PATIENTS: Children from 0 to 18 years with symptoms compatible with Covid-19 of ≤5 days of duration were included. Two NPS samples (Ag-RDT and RT-PCR) and one OSS sample for RT-PCR were collected. MAIN OUTCOME: Performance of Ag-RDT and RT-PCR on NPS and RT-PCR on OSS sample for SARS-CoV-2. RESULTS: 1174 children were included, aged 3.8 years (IQR 1.7-9.0); 73/1174 (6.2%) patients tested positive by at least one of the techniques. Sensitivity and specificity of OSS RT-PCR were 72.1% (95% CI 59.7 to 81.9) and 99.6% (95% CI 99 to 99.9), respectively, versus 61.8% (95% CI 49.1 to 73) and 99.9% (95% CI 99.4 to 100) for the Ag-RDT. Kappa index was 0.79 (95% CI 0.72 to 0.88) for OSS RT-PCR and 0.74 (95% CI 0.65 to 0.84) for Ag-RDT versus NPS RT-PCR. CONCLUSIONS: RT-PCR on the OSS sample is an accurate option for SARS-CoV-2 testing in children. A less intrusive technique for younger patients, who usually are tested frequently, might increase the number of patients tested.

[Patient with respiratory compromise controlled by a pediatric home hospitalization unit.] / Paciente con compromiso respiratorio controlado por una unidad pediátrica de hospitalización a domicilio.

OBJECTIVE: The use of paediatric home oxygen therapy is initiated in neonatal chronic lung disease; later it spreads to other patients with chronic hypoxemia. The frequency and need for oxygen therapy is growing; this, together with the family benefits, justify the implementation of a home treatment plan. Our objective with this work was to know and describe the characteristics of the patients admitted to the Pediatric HaD Unit of a tertiary hospital, the average cost per patient of oxygen therapy during 13 years of review, and evaluate the quality of the service. METHODS: Retrospective descriptive study by reviewing records of patients admitted to home care hospital at home of a paediatric tertiary care hospital (n=124) for 13 years (2000-2013), to learn and to describe the characteristics of the unit and these patients, and costs. After that, it was done statistical analysis through t-Student. RESULTS: 124 patients with chronic hypoxemia patients with mean age of 2.2 years. The most frequent cause was lung diseases, including ECPN as the most important. They accounted 14.2% of hospitalizations in home care hospital at home department, and 60% were achieved clinical stability. The mean cost was 1,991.1€ per patient, which supposes 93% of economical saving in comparison with conventional hospitalization (3,988.91€). CONCLUSIONS: The use of oxygen in HaD improves the quality of life and survival of our patients, reducing the number of readmissions and hospital costs.

OBJETIVO: El empleo de oxigenoterapia domiciliaria pediátrica se inicia en la enfermedad pulmonar crónica neonatal (EPCN), extendiéndose posteriormente a otros pacientes con hipoxemia crónica. La frecuencia y necesidad de oxigenoterapia está en crecimiento, esto, junto a los beneficios familiares, justifican la implantación de un plan de tratamiento domiciliario. Nuestro objetivo con este trabajo fue conocer y describir las características de los pacientes ingresados en la Unidad de HaD Pediátrica de un hospital de tercer nivel, el coste medio por paciente de la oxigenoterapia durante 13 años de revisión, y evaluar la calidad del servicio. METODOS: Estudio descriptivo retrospectivo mediante revisión de las historias de los pacientes ingresados en hospitalización a domicilio pediátrica (HaD) de un hospital de tercer nivel (n=124) durante 13 años (2000-2013), con descripción de las distintas características de la unidad, los pacientes incluidos y el coste. Posteriormente, se realizó análisis estadístico con t-Student. RESULTADOS: Se analizaron 124 pacientes con hipoxemia crónica, con una edad media de 2,2 años, siendo la causa más frecuente las enfermedades pulmonares y entre ellas la EPCN. Estos pacientes representaron el 14,2% de los ingresos en HaD, y en el 60% fue posible la retirada de la oxigenoterapia por buena evolución clínica. El Coste total medio por paciente fue de 1.991,1€, lo que supone un ahorro respecto a la modalidad de hospitalización convencional (3.988,91€) del 93% en nuestro centro. CONCLUSIONES: El uso de oxígeno en HaD mejora la calidad de vida y supervivencia de nuestros pacientes, disminuyendo el número de reingresos y costes hospitalarios.

Isolated Growth Hormone Deficiency and Idiopathic Short Stature: Comparative Efficiency after Growth Hormone Treatment up to Adult Height.

INTRODUCTION: Treatment with growth hormone (GH) is not approved for idiopathic short stature (ISS) in Europe. OBJECTIVES: To compare the growth of children treated with isolated GH deficiency (IGHD) vs. ISS-treated and untreated children. METHODS: A retrospective descriptive study of patients treated in the last 14 years for IGHD (Group A), in comparison with ISS-treated (Group B) and untreated (Group C) subjects. RESULTS: Group A had 67 males, who showed a height gain of 1.24 SD. Group B had 30 boys, who showed a height gain of 1.47 SD. Group C had 42 boys, who showed an improvement of 0.37 SD. The final heights were -1.52 SD, -1.31 SD, and -2.03 SD, respectively. Group A and C did not reach their target heights (with differences of 0.27 SD and 0.59 SD, respectively). Group B surpassed their target height by 0.29 SD. CONCLUSIONS: The final heights of the IGHD and treated ISS are similar. Treated groups were taller than untreated groups.

Good Metabolic Control in Children with Type 1 Diabetes Mellitus: Does Glycated Hemoglobin Correlate with Interstitial Glucose Monitoring Using FreeStyle Libre?

BACKGROUND: Good metabolic control of Type 1 diabetes (T1D) leads to a reduction in complications. The only validated parameter for establishing the degree of control is glycated hemoglobin (HbA1c). We examined the relationship between HbA1c and a continuous glucose monitoring (CGM) system. MATERIALS AND METHODS: A cohort prospective study with 191 pediatric patients with T1D was conducted. Time in range (TIR), time below range (TBR), coefficient of variation (CV), number of capillary blood glucose tests, and HbA1c before sensor insertion and at one year of use were collected. RESULTS: Patients were classified into five groups according to HbA1c at one year of using CGM. They performed fewer capillary blood glucose test at one year using CGM (-6 +/- 2, p < 0.0001). We found statistically significant differences in TIR between categories. Although groups with HbA1c < 6.5% and HbA1c 6.5-7% had the highest TIR (62.214 and 50.462%), their values were highly below optimal control according to CGM consensus. Groups with TBR < 5% were those with HbA1c between 6.5% and 8%. CONCLUSIONS: In our study, groups classified as well-controlled by guidelines were not consistent with good control according to the CGM consensus criteria. HbA1c should not be considered as the only parameter for metabolic control. CGM parameters allow individualized targets.

Differences between patients with isolated GH deficiency based on findings in brain magnetic resonance imaging.

INTRODUCTION: Protocol for prescribing hormone replacement therapy in isolated growth hormone (GH) deficiency includes magnetic resonance imaging of the brain. There is controversy on the frequency of structural pituitary abnormalities and on the importance of abnormal MRI findings on prognosis and response to GH replacement. METHODS: A descriptive, retrospective study of children of both sexes aged 0-14 years, who had undergone brain MRI, diagnosed with isolated GH deficiency at a tertiary hospital in the past 14 years, aimed at reporting the frequency of abnormal MRI findings in isolated GH deficiency, and to establish whether differences exist in height diagnosis and evolution according to MRI findings. MRI findings were also compared with the findings reported in healthy children in order to establish incidence. RESULTS: 96 patients were studied, of whom 74/96 (77%) reached adult age. Abnormal MRI findings were seen in 11.5% of them (8/11 of pituitary origin). No brain or pituitary tumor was seen in any case. Patients with abnormal images had a mean age at treatment start of 8 years, a target height of -0.8SD, and a final height of 1.04SD, while patients with normal MRI findings had an age at treatment start of 10 years old, a target height of -1.44SD, and a final height of -1.75SD, with statistically significant differences. CONCLUSIONS: Patients with abnormal MRI findings show a more favorable response to GH replacement therapy.

[Efficacy and safety of replacement treatment in isolated growth hormone deficiency]. / Eficacia y seguridad del tratamiento sustitutivo en el déficit aislado de hormona del crecimiento.

INTRODUCTION: Growth in patients with isolated growth hormone (GH) deficiency is heterogeneous despite treatment due to the low specificity of diagnostic tests, making it necessary to define efficacy variables. AIMS: To evaluate efficacy of hormone replacement therapy in children with isolated GH deficiency. METHODS: Observational-ambispective study of patients treated in our department in the last 14 years for isolated GH deficiency. This was defined as a GH level less than 7.4mg/dl in response to 2 stimulation tests in patients with height<2SD and a decreased growth rate. RESULTS: The study included a total 97 patients, of whom 69% were boys. The large majority (89.58%) achieved final height. None of them had side effects. The median dose of GH used was 0.028mg/kg/day (0.03-0.025). There was a gain of 1.17 SD in final height. Around three-quarters (71.13%) of the patients were reassessed in adulthood, of whom 39.4% maintained the deficiency, and 79.31% achieved target range height. Target height, estimated height, and the total pubertal gain were positively correlated with final height, while the bone age/chronological age ratio and the initial insulin-like growth factor-1 showed a negative correlation. CONCLUSIONS: A majority of patients reached target size, although only a few of them maintained the deficiency in adulthood. Target size, estimated adult height, and pubertal variables are directly related to adult height, while bone age/chronological age and insulin-like growth factor-1 were inversely related, and these can be used as efficacy variables. No adverse effects were observed in the sample with the doses used for the treatment.