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Growth hormone deficiency (GHD) describes the impairment of growth hormone (GH) secretion by the pituitary somatotroph cells. GHD may be congenital, with causes, including genetic alterations and structural brain malformations, or acquired, including midline tumours, cranial irradiation, traumatic brain injury, central nervous system infections and inflammatory conditions. GHD in children is characterised by short stature, delayed bone maturation and abnormalities in substrate metabolism, body composition, physical and psychosocial functioning, all of which improve with recombinant human GH (rhGH) therapy. The diagnosis of GHD is based on clinical signs and symptoms, biochemistry and imaging. Although GH stimulation tests are considered the mainstay of diagnostic investigations, the results must be interpreted with caution owing to the variability in cut-off values and reproducibility. Transition refers to the physical and psychosocial changes in adolescent patients during the mid-teens to late teens (usually 15–18 years of age) until about 6–7 years after achievement of adult height. During the transition age, only a small residual capacity of longitudinal growth is left, but body maturity is not yet complete. Discontinuation of rhGH treatment at the end of longitudinal growth in adolescents with permanent GHD is associated with decreased muscle strength and mass, increased body fat (mainly in the abdomen), the arrest or reversal of muscle mass and bone mass density (BMD) gain and lipid profile deterioration. For these reasons, patients whose GHD persists during the transition age need to continue rhGH treatment to obtain full somatic maturation and normalisation of body composition, BMD, quality of life (QoL) and lipid metabolism. There is some evidence that rhGH treatment during transition may result in improved growth and bone health, as well as a better prognosis for metabolic and cardiovascular risks in the long term. Since these patients need to continue treatment to complete their body development, a multidisciplinary approach is required to ensure continuity of care during the transfer from paediatric to adult endocrinology services. Guidelines for the diagnosis and treatment of young adults with GHD have been published by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), Endocrine Society, European Society of Paediatric Endocrinology (ESPE), Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society and Endocrine Society of Australia. However, clinical practice lacks uniformity in terms of diagnosis and treatment of transition-age patients, the impact of GH replacement during transition has not been adequately assessed in randomised clinical trials (RCTs), validated questionnaires to assess QoL in patients on rhGH treatment in the transition period are not available and there is still uncertainty about the multidisciplinary approach during transition [8]. Hence, a structured transition protocol is essential to establish the best practice for transitioning adolescents with GHD to adult care. A study in Italy in 2015 identified a low level of awareness of these issues in clinical practice and real-world gaps in the management of GHD patients during transition. To address these gaps and assist endocrinologists (adult and paediatric) in the diagnosis and treatment of GHD in transition-age patients, a Delphi consensus process was undertaken to develop clinically relevant recommendations. The current consensus statements address the diagnosis of GHD, benefits of treatment, monitoring and management of transition-age patients with GHD, along with treatment adherence and safety concerns.

In the published article, there was an error in affiliation(s) 29. Instead of “Departement of Pediatrics, Diabetes Research Institute, IRCCS San Raffaele, Milano, Italy”, it should be “Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy”. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

BACKGROUND: Congenital hypothyroidism (CH) is the most common congenital endocrine disease with reported high prevalence of associated congenital anomalies which are also present in case of congenital cytomegalovirus (cCMV) infection. SUBJECTS AND METHODS: We present two cases of newborns cCMV infection with CH. In the first case thyroid agenesis was diagnosed and cCMV infection was also confirmed for the hypotonia persistence after L-thyroxine treatment. In the second case thyroid dyshormonogenesis was diagnosed with maternal CMV serological conversion in the first trimester of gestation and confirmed post-neonatal infection. Incidence of CH has increased in the Italian region of Piedmont in the years 2014-2019 up to 1:1090 with higher incidence of cCMV infection in the babies with diagnosis of CH (12/1000 vs. 5-7/1000 in the newborns without CH). To our knowledge, no data on the association of cCMV infection with a CH condition have been reported in the literature to date. CONCLUSIONS: The described cases could be useful to alert caregivers in case of maternal seroconversion to avoid maternal and foetal hypothyroidism. On the other hand, when the clinical condition of newborns with CH diagnosis do not improve after l-thyroxine treatment, it might be important to consider cCMV infection.

OBJECTIVE: To study the prevalence of congenital syphilis and its risk factors in Italy. STUDY DESIGN: Prospective study from 1 July 2006 to 30 June 2007. Data on mother-child pairs were collected for every syphilis seropositive mother. RESULTS: Maternal syphilis seroprevalence at delivery was 0.17%. 207 infants were born to 203 syphilis seropositive mothers. In 25 newborns it was possible to diagnose congenital syphilis (20/100,000 live births). Maternal risk factors included age

In order to identify the molecular basis of phenylketonuria (PKU) in Italy, we screened the entire coding sequence of the phenylalanine hydroxylase gene in 20 Italian PKU patients, whose origins are scattered throughout Italy. The frequency of each identified mutation and of 5 other European mutations was determined within a panel of 92 Italian PKU patients. This approach allowed us to identify 20 different PKU mutations and characterize 64% of the Italian PKU chromosomes. Eleven mutations (IVS10nt546, L48S, R158Q, R261Q, P281L, R261X, R252W, delta T55, IVS7nt1, IVS12nt1, Y414C) represent 55.4% of the Italian PKU alleles, the most common mutations being IVS10nt546 (12.4%) and L48S (9%). All the other mutations are very rare. These data confirm the great heterogeneity expected from previous RFLP haplotype studies. Genotype/phenotype correlation allowed for assessment of the clinical impact of the 20 identified mutations.

BACKGROUND: Genetic and epigenetic alterations in the GNAS locus are responsible for the Gsα protein dysfunctions causing Pseudohypoparathyroidism (PHP) type Ia/c and Ib, respectively. For these heterogeneous diseases characterized by multiple hormone resistances and Albright's Hereditary Osteodystrophy (AHO) the current classification results inadequate because of the clinical overlap between molecular subtypes and a standard clinical approach is still missing. In the present paper several members of the Study Group Endocrine diseases due to altered function of Gsα protein of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) have reviewed and updated the clinical-molecular data of the largest case series of (epi)/genetically characterized AHO/PHP patients; they then produced a common healthcare pathway for patients with these disorders. METHODS: The molecular analysis of the GNAS gene and locus identified the causal alteration in 74 subjects (46 genetic and 28 epigenetic mutations). The clinical data at the diagnosis and their evolution during up to 15 years follow-up were collected using two different cards. RESULTS: In patients with genetic mutations the growth impairment worsen during the time, while obesity prevalence decreases; subcutaneous ossifications seem specific for this group. Brachydactyly has been detected in half of the subjects with epigenetic alterations, in which the disease overts later in life, often with symptomatic hypocalcaemia, and also early TSH and GHRH resistances have been recorded. CONCLUSIONS: A dedicated healthcare pathway addressing all these aspects in a systematic way would improve the clinical management, allowing an earlier recognition of some PHP features, the optimization of their medical treatment and a better clinical-oriented molecular analysis. Furthermore, standardized follow-up data would provide new insight into less known aspects.

Background Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. Results The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

Background X-linked hypophosphatemic rickets (XLH) is the first cause of inherited hypophosphatemia and is caused by mutation in the PHEX gene, resulting in excessive expression of the phosphaturic factor FGF23. Symptoms are mainly related to rickets in children and osteomalacia in adults and cause several complications that can be highly invalidating. Due to its rarity, XLH is poorly known and diagnosis is frequently delayed. Conventional treatment is based on oral phosphate salts supplementation and activated vitamin D analogs, which however, cannot cure the disease in most cases. Objective Due to the low prevalence of XLH, an experts’ opinion survey was conducted across Italian centers to collect data on XLH and on its management. Methods A questionnaire was developed by a group of experts to collect data on XLH epidemiology, diagnosis and treatment in Italy. Results Data from 10 Italian centers (nine of which pediatric) on 175 patients, followed between 1998 and 2017, were included in the survey. Most patients were followed since childhood and 63 children became adults during the investigated period. The diagnosis was made before the age of 1 and between 1 and 5 years in 11 and 50% of cases, respectively. Clinically apparent bone deformities were present in 95% of patients. These were ranked moderate/severe in 75% of subjects and caused growth stunting in 67% of patients. Other frequent complications included bone pain (40%), dental abscesses (33%), and dental malpositions (53%). Treatment protocols varied substantially among centers. Nephrocalcinosis was observed in 34% of patients. Tertiary hyperparathyroidism developed in 6% of patients. Conclusions XLH remains a severe condition with significant morbidities.

Background Prader–Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients’ care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.

SHOX haploinsufficiency causes 70–90% of Léri-Weill dyschondrosteosis (LWD) and 2–10% of idiopathic short stature (ISS). Deletions removing the entire gene or enhancers and point mutations in the coding region represent a well-established cause of haploinsufficiency. During diagnostic genetic testing on ISS/LWD patients, in addition to classic SHOX defects, five 5′UTR variants (c.-58G > T, c.-55C > T, c.-51G > A, c.-19G > A, and c.-9del), were detected whose pathogenetic role was unclear and were thus classified as VUS (Variants of Uncertain Significance). The purpose of the present study was to investigate the role of these noncoding variations in SHOX haploinsufficiency. The variants were tested for their ability to interfere with correct gene expression of a regulated reporter gene (luciferase assay). The negative effect on the mRNA splicing predicted in silico for c.-19G > A was assayed in vitro through a minigene splicing assay. The luciferase assay showed that c.-51G > A, c.-19G > A, and c.-9del significantly reduce luciferase activity by 60, 35, and 40% at the homozygous state. Quantification of the luciferase mRNA showed that c.-51G > A and c.-9del might interfere with the correct SHOX expression mainly at the post-transcriptional level. The exon trapping assay demonstrated that c.-19G > A determines the creation of a new branch site causing an aberrant mRNA splicing. In conclusion, this study allowed us to reclassify two of the 5′UTR variants identified during SHOX diagnostic screening as likely pathogenic, one remains as a VUS, and two as likely benign variants. This analysis for the first time expands the spectrum of the genetic causes of SHOX haploinsufficiency to noncoding variations in the 5′UTR.

The paper investigates the problem of Soil-Foundation-Structure Interaction (SFSI) for buildings supported on piles through the comparative analysis between the fixed base and the compliant base assumptions. The structure, a nine-storey residential building (with or without infills), is modelled in non-linear regime while the piled foundation is idealized by means of independent lumped parameters models, either linear or non-linear. In this last case, the soil-foundation system is replaced by an assembly of viscous-dampers, fictitious masses and non-linear springs modelled according to the classical Bouc-Wen formulation, so as to account for the hysteretic behaviour of the foundation. A detailed calibration procedure for both linear and non-linear foundation models is also presented and discussed. Two different natural soil deposits are considered, a pyroclastic deposit and a deep layer of lacustrine clay. The results undertaken in the context of a probabilistic analysis show that SFSI may lead to a significant reduction of the seismic demand in infilled buildings at low and intermediate earthquake intensity levels. Conversely, at higher intensity earthquakes the seismic demand is not affected by the non-linear springs. It is shown that a proper modelling of radiation mechanism at foundation level is crucial for a reliable and sustainable prediction of SFSI effects.

Background/ObjectivesThe present study aimed to validate the Italian version of the Hyperphagia Questionnaire (HQ), a 11-items questionnaire developed to assess hyperphagia in individuals with Prader-Willi syndrome (PWS). This is a complex neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity.MethodsParents of 219 individuals with PWS (age range 3–54 years; Mage = 17.90; 108 Males), recruited in 12 hospitals in Italy responded to HQ during routine visits. In function of the level of analyses the sample was divided into two subgroups ( years) or into four age-subgroups (2.5–4.5; 4.5–8; 8–18; >18 years) corresponding to different clinical stages.ResultsConfirmatory factor analysis (CFA) confirmed the three hyperphagic subdimensions of the original structure (behavior, drive, and severity), but one item was dropped out, reducing the final version to 10 items. Using multi-group CFA, HQ showed satisfactory indexes of measurement invariance by age. Good indexes of internal consistency (Cronbach's alpha and McDonald's Omega coefficients) were found for each subdimension. The three hyperphagia subdimensions positively converged with other food-related measures: emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. A significant increase of all hyperphagic subdimensions was found across age groups. Higher hyperphagic levels were found in participants with higher body mass index. Hyperphagic drive differently increased in function of the interaction between age and underlying genetic mechanisms.ConclusionThe Italian version of the HQ is a psychometrically valid and reliable instrument for assessing hyperphagia in individuals with PWS. This tool may prove useful to evaluate the efficacy of pharmacologic and rehabilitative treatments.

Puberty represents a milestone during a person's life and is characterized by several physical and psychological changes which end with the achievement of sexual maturation and of fertility. Puberty onset depends on a series of sophisticated, not completely understood, mechanisms certainly involving Gonadotropin-Releasing Hormone (GnRH) and its effects on pituitary gonadotropins. As recent evidence has demonstrated that pubertal timing deeply affects future adult health life, many efforts have been performed in order to clarify the exact actors involved in the onset and progression of puberty. Genetic factors are undoubtedly essential players in the regulation of pubertal development, accounting for approximately 50-80% of its variability. Mutations in genes such as KISS1, MKRN3, and DLK1 have been associated with central precocious puberty. Interestingly, a possible involvement of epigenetic mechanisms has been proposed as additional element able to affect pubertal phase. Environmental factors have recently attracted much attention. Indeed, an overall decrease in the age of puberty has been observed in the last decades. As genetic factors require long time to exert their effect, other players, such as environmental ones, may be involved. Special focus has been posed on nutritional status, endocrine-disrupting chemicals with non-conclusive results. Pubertal timing deeply affects future life, suggesting the need to clarify mechanisms driving pubertal onset and progression, in order to identify tailored therapeutic strategies and targets.

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Background: An ENDO-European Reference Network (ERN) initiative was launched that was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis, and management of primary and central CH. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Summary: The recommendations include the various neonatal screening approaches for CH as well as the etiology (also genetics), diagnostics, treatment, and prognosis of both primary and central CH. When CH is diagnosed, the expert panel recommends the immediate start of correctly dosed levothyroxine treatment and frequent follow-up including laboratory testing to keep thyroid hormone levels in their target ranges, timely assessment of the need to continue treatment, attention for neurodevelopment and neurosensory functions, and, if necessary, consulting other health professionals, and education of the child and family about CH. Harmonization of diagnostics, treatment, and follow-up will optimize patient outcomes. Lastly, all individuals with CH are entitled to a well-planned transition of care from pediatrics to adult medicine. Conclusions: This consensus guidelines update should be used to further optimize detection, diagnosis, treatment, and follow-up of children with all forms of CH in the light of the most recent evidence. It should be helpful in convincing health authorities of the benefits of neonatal screening for CH. Further epidemiological and experimental studies are needed to understand the increased incidence of this condition.

Annular shaped pile groups are a very common foundation layout for onshore wind turbines and other slender structures. In this study, their performance under vertical loads of moderate to high eccentricity, including moment rotation response and bearing capacity, was investigated by centrifuge testing on small scale physical models embedded in kaolin clay. To identify experimentally the capacity of the examined pile groups under different load paths, the model foundations were loaded monotonically until a clear collapse mechanism was achieved. The testing procedure and the proposed interpretation methodology can be easily adapted to load paths or pile layouts other than those considered in the current study. The experimental data can be adopted as a useful benchmark for mathematical models aimed at predicting the response of pile groups to complex load paths. The results of this testing program can also be used to assess the degree of conservatism of current methods adopted by industry for the design of piled foundations subjected to eccentric loads.

The problem of failure envelopes of pile groups subjected to vertical and eccentric load is investigated both theoretically and experimentally. A critical review of literature works on failure envelopes for pile groups under combined axial-moment loading is first provided. Emphasis is placed on a recent, exact solution derived from theorems of limit analysis by idealizing piles as uniaxial rigid-perfectly plastic elements. The application of the relevant equations over a practical range of problems needs only the axial capacities in compression and uplift of the isolated piles. An intense program of centrifuge experiments carried out along with different load paths on annular shaped pile groups aimed at validating the equations pertinent to the above solution is presented and discussed. The endpoints of the load paths followed in the centrifuge lie approximately above the analytical failure envelope, giving confidence that the reference equations can be reliably adopted to assess the capacity of a pile group under combined axial-moment loading. Finally, the kinematics of the collapse mechanism observed experimentally is compared to that determined from the application of the reference theory.

INTRODUCTION: Subjects with hypo- or hypergonadotropic hypogonadism need hormone replacement therapy (HRT) to initiate puberty and maintain it with a normal hormonal status. While general recommendations for the management of HRT in adults have been published, no systematic suggestions focused on adolescents and young adults. The focus of this review is the HRT in males and females with hypogonadism, from puberty to late reproductive age, covering the different management options, encompassing sex steroid or gonadotropin therapy, with discussion of benefits, limitations and specific considerations of the different treatments. EVIDENCE ACQUISITION: We conducted an extensive search in the 3 major scientific databases (PubMed, EMBASE and Google Scholar) using the keywords "hormonal replacement therapy," "hypogonadism," "bone mineral density," "estradiol/testosterone," "puberty induction," "delayed puberty." Case-control studies, case series, reviews and meta-analysis published in English from 1990 to date were included. EVIDENCE SYNTHESIS: By considering the available opportunities for fertility induction and preservation, we hereby present the proposals of practical schemes to induce puberty, and a decisional algorithm to approach HRT in postpubertal adolescents. CONCLUSIONS: A condition of hypogonadism can underlie different etiologies involving the hypothalamic-pituitary-gonadal axis at different levels. Since the long-terms effects of hypogonadism may vary and include not only physical outcomes related to sex hormone deficiencies, but also psychological problems and implications on fertility, the initiation, maintenance and consolidation of puberty with different pharmaceutical options is of utmost importance and beside pubertal development, optimal uterine and testicular growth and adequate bone health should consider also the psychosocial wellbeing and the potential fertility.

Objective To evaluate the prevalence and natural course of autoimmune and non-autoimmune subclinical hypothyroidism (SH) in Down syndrome (DS) children and adolescents. Design Prospective multicenter study. Methods For the study, 101 DS patients with SH (TSH 5–10 mIU/L; FT4 12–22 pmol/L), aged 2–17 years at SH diagnosis were enrolled. Annual monitoring of TSH, FT4, BMI, height, and L-thyroxine dose was recorded for 5 years. Thyroid autoimmunity was tested at diagnosis and at the end of follow-up. Results Thirty-seven out of 101 patients displayed autoantibody positivity (group A); the remaining 64 were classified as non-autoimmune SH (group B). Group A was characterized by higher median age at SH diagnosis and by more frequent family history of thyroid disease (6.6 vs 4.7 years, P = 0.001; 32.4% vs 7.8%, P = 0.001 respectively), whereas congenital heart defects were more common in group B (65.6% vs 43.2%, P = 0.028). Gender, median BMI (SDS), height (SDS), FT4, and TSH were similar in both groups. At the end of follow-up: 35.1% of group A patients developed overt hypothyroidism (OH) vs 17.2% of group B (P = 0.041); 31.25% of group B vs 10.8% of group A became biochemically euthyroid (P = 0.02); and 37.8% of group A vs 51.5% of group B still had SH condition (P = 0.183). Logistic regression suggested autoimmunity (OR = 3.2) and baseline TSH values (OR = 1.13) as predictive factors of the evolution from SH to OH. Conclusions In DS children, non-autoimmune SH showed higher prevalence and earlier onset. The risk of thyroid function deterioration over time seems to be influenced by thyroid autoimmunity and higher baseline TSH values.

This work investigates the role of foundation type and layout on the seismic response of a bridge pier. Reference is made to an Italian case study of a bridge pier to be founded on a well-characterized subsoil. Both a caisson and a 3×3 pile foundation are considered as suitable design options. For each foundation type, three different geometrical layouts satisfying Ultimate Limit State (ULS) checks are analysed. Equivalent-linear ground response analyses are preliminary performed to derive the mobilized soil stiffness and damping ratio. FE analyses of the complete soil-foundation-bridge pier model are then carried out. Results indicate that consideration of Soil-Structure Interaction effects strongly reduces the pier acceleration, especially for pile foundations, which allow for a higher dissipation of energy due to radiation damping. Further, the role of foundation type and layout is discussed by separating the kinematic and inertial components of interaction, with reference to both frequency and time domain response. Some considerations about possible simplifying assumptions to account for these effects in routine engineering are finally reported.