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Abstract The primary objective of this study was to evaluate the prevalence of low femoral and lumbar spine bone mineral density (BMD) in adults with arthrogryposis multiplex congenita (AMC). We performed a retrospective cohort analysis of adults with AMC who were enrolled in the French Reference Center for AMC and in the Pediatric and Adult Registry for Arthrogryposis (PARART, NCT05673265). Patients who had undergone dual-energy X-ray absorptiometry (DXA) and/or vitamin D testing were included in the analysis. Fifty-one patients (mean age, 32.9 ± 12.6 years) were included; 46 had undergone DXA. Thirty-two (32/51, 62.7%) patients had Amyoplasia, and 19 (19/51, 37.3%) had other types of AMC (18 distal arthrogryposis, 1 Larsen). Six patients (6/42, 14.3%) had a lumbar BMD Z score less than − 2. The mean lumbar spine Z score (− 0.03 ± 1.6) was not significantly lower than the expected BMD Z score in the general population. Nine (9/40, 22.5%) and 10 (10/40, 25.0%) patients had femoral neck and total hip BMD Z scores less than − 2, respectively. The mean femoral neck (− 1.1 ± 1.1) and total hip (− 1.2 ± 1.2) BMD Z scores in patients with AMC were significantly lower than expected in the general population (p

Este artículo traza la trayectoria biográfica de una vivienda arqueológica situada temporalmente en la se- gunda mitad del primer milenio DC. Dicho análisis busca aportar al conocimiento del rol de los espacios domésticos en la estructuración, producción y reproducción de la vida aldeana en la cuenca media de la vertiente oriental de Sierra de El Alto-Ancasti (Catamarca, Argentina), en la que se ubica el caso de estu- dio. La reconstrucción de la secuencia de estratigrafía arqueológica permite observar un proceso dinámico de producción de los espacios de vivienda, donde un mismo recinto puede ser cocina, cobertizo, espacio de actividades múltiples a cielo abierto, basural o recinto techado. Al final del trabajo se expone la lógica y la temporalidad implicada en la producción de los espacios de la casa y su participación en la producción de los paisajes aldeanos hallados en la región de estudio.

Las técnicas de aplicación de las pinturas rupestres resultan fundamentales para comprender sus procesos de producción, pues permiten acceder a las interacciones constitutivas entre seres, materiales, tiempos y espacios que se entablan al hacer los motivos. Sin embargo, son escasas las investigaciones centradas en identificar marcadores materiales específicos que permitan diferenciar entre la multiplicidad de técnicas de aplicación posibles. En líneas generales, estas se han inferido a partir de criterios poco explicitados. Este trabajo plantea un abordaje experimental de cuatro técnicas de aplicación (digital, con hisopo, con pincel y con palito) con vistas a detectar huellas específicas a cada una. Posteriormente, se aplican estos conocimientos para avanzar en el relevamiento macroscópico de las pinturas rupestres de la cueva de La Candelaria (departamento Ancasti, Catamarca). Ello posibilitó identificar huellas de diversas técnicas de aplicación en las pinturas del sitio, demostrando la importancia de retroalimentar los relevamientos in situ con estudios experimentales.

Context: The 2019 American Association of Clinical Endocrinologists guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase., Objective: The aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement., Patients and Methods: Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST, and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies) and 18 severe organic GHD (≥3 hormone deficiencies)., Results: Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis identified 7.3 μg/L as the optimal GH peak cutoff to GST [95% confidence interval (CI) 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value (PPV) 88.0%, negative predictive value (NPV) 95.7%] able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3 hormone deficiencies showed a GH peak <5 μg/L at ITT and <5.8 μg/L at GST but 1. The optimal cutoff for IGF-1 was -1.4 SD score (95% CI -1.94 to 0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population., Conclusion: A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pretest probability of permanent GHD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Knee popping is a frequent symptom among knee disorders which requires further investigation in case of a recent evolution of the symptom or pathological associated ones. This article reports a rare presentation of pigmented villonodular synovitis (PVNS), identified as the cause of knee popping symptoms, by performing MRI sequences at various degrees of knee flexion for a patient complaining from a gradual onset of knee popping, occurring when bending the knee over 120° of flexion. MRI sequences were performed just before the popping occurs (flexion 90°) and right after it had occurred (flexion 120°). The latter confirmed the origin of the symptom as the lesion moved forward, passing brutally through the interstice between the PCL and the ACL at 120° of flexion, explaining the popping. Treatment decision was to perform an arthroscopic resection of the lesion. Diagnosis of isolated PVNS was confirmed after anatomopathological analysis., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Context: Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased., Objective: To compare the incidence of idiopathic central precocious puberty (ICPP) during COVID-19 with that of the previous 4 years., Methods: Anthropometric, biochemical, and radiological parameters were collected between January 2016 and June 2021 from 133 girls who met the Rapidly Progressive ICPP criteria (RP-ICPP)., Results: We found a higher incidence of RP-ICPP between March 2020 and June 2021 (group 2) compared with January 2016 through March 2020 (group 1) (53.5% vs 41.1%); 2021 showed the highest annual incidence ( P < .05). Group 1 and group 2 differed in age at diagnosis (7.96 ± 0.71 vs 7.61 ± 0.94; P < .05), mean Tanner stage (2.86 ± 0.51 vs 2.64 ± 0; P < .05), and in the time between the appearance of thelarche and diagnosis (0.93 ± 0.75 vs 0.71 ± 0.62 years, P < .05). There was an increase in the number of girls aged <8 years in group 2 and a significantly higher number of girls aged >8 years was found in group 1 (42 in group 1 vs 20 in group 2, P < 0.05). Overall body mass index SD score showed higher values ​​in group 2 (1.01 ± 1.23 vs 0.69 ± 1.15; P = .18), which spent an average of 1.94 ± 1.81 hours per day using electronic devices; 88.5% of this group stopped any physical activity., Conclusions: A spike in new diagnoses of idiopathic (1.79-fold higher) and RP-CPP coincided with the COVID-19 pandemic. The incidence of RP-ICPP was 1.3-fold higher during COVID-19 with a trend toward an increase in body mass index SD score. The expanding use of digital devices and the reduction of daily physical activity represent possible risk factors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: The etiology of central precocious puberty (CPP) includes a spectrum of conditions. Girls younger than age 6 years with CPP should undergo cranial magnetic resonance imaging (MRI), but it remains controversial whether all girls who develop CPP between the ages of 6 and 8 years require neuroimaging examination., Objective: To investigate the frequency of brain MRI abnormalities in girls diagnosed with CPP and the relationship between maternal factors, their age at presentation, clinical signs and symptoms, hormonal profiles, and neuroimaging findings., Methods: Data were collected between January 2005 and September 2019 from 112 girls who showed clinical pubertal progression before 8 years of age who underwent brain MRI., Results: MRI was normal in 47 (42%) idiopathic (I) scans, 54 (48%) patients had hypothalamic-pituitary anomalies (HPA) and/or extra-HP anomalies (EHPA), and 11 (10%) had brain tumors or tumor-like conditions (BT/TL), including 3 with neurological signs. Associated preexisting disorders were documented in 16. Girls with BT/TL had a higher LH peak after GnRH test (P = 0.01) than I, and those older than age 6 years had a higher craniocaudal diameter of the pituitary gland (P = 0.01); their baseline FSH and LH (P = 0.004) and peak FSH (P = 0.01) and LH (P = 0.05) values were higher than I. Logistic regression showed maternal age at menarche (P = 0.02) and peak FSH (P = 0.02) as BT/TL risk factors., Conclusions: MRI provides valuable information in girls with CPP by demonstrating that fewer than half have a normal brain MRI and that few can have significant intracranial lesions after the age of 6, despite the absence of suggestive neurological signs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development., Design Patients and Methods: Children detected by neonatal screening were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Low) or 12.6-15 μg/kg/day (High). All patients underwent periodical clinical examination with measurement of growth parameters and measurement of TSH and FT4. Neurocognitive development was evaluated at the age of 24 months using Griffiths Mental Development Scales (GMDS) and cognitive and behavioral assessment was performed at 48 months of age using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The study was registered with clinicaltrials.gov (NCT05371262)., Results: Treatment schemes below or above 12.5 μg/kg/day were both associated with rapid normalization of TSH and thyroid hormone levels in most patients with no differences in the risk of over- and under-treatment episodes in the first months of life. Growth parameters were normal and comparable between the two groups. Developmental quotients at 24 months of age were normal in both groups (Low 100.6 ± 15.5 vs High 96.9 ± 16.6). Likewise, at 4 years of age IQ and subtest scores were comparable between patients from Low and High (Total IQ 104.2 ± 11.4 vs 101.0 ± 20.3, Verbal IQ 103.9 ± 11.5 vs 98.7 ± 15.1, Performance IQ 105.3 ± 10.4 vs 100.3 ± 19.8). 6/45 CH patients (13.3%) showed a total IQ below 85 (73.7 ± 5.9) regardless of age at diagnosis, L-T4 starting dose, time of FT4 and TSH normalization and episodes of over and undertreatment. Worse socioeconomic status and delayed bone age at diagnosis were the only predictors of an increased risk of having suboptimal IQ at 24 and IQ at 48 months., Conclusions: Our results indicate that initial treatment with L-T4, 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, are both associated with normal growth and neurodevelopmental outcomes in children with CH detected by neonatal screening. Further studies with a long-term follow-up on a larger number of patients are needed to confirm these results., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05371262?term=NCT05371262&draw=2&rank=1 identifer NCT05371262., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Esposito, Vigone, Polizzi, Wasniewska, Cassio, Mussa, Gastaldi, Di Mase, Vincenzi, Pozzi, Peroni, Bravaccio, Capalbo, Bruzzese and Salerno.)

Context: Data on pubertal timing in Silver Russell syndrome (SRS) are limited., Design and Methods: Retrospective observational study including twenty-three SRS patients [11p15 loss of methylation, (11p15 LOM, n=10) and maternal uniparental disomy of chromosome 7 (mUPD7, n=13)] and 21 small for gestational age (SGA). Clinical (thelarche in females; testis volume ≥ 4 ml in males; pubarche), BMI SD trend from the age of 5 to 9 years to the time of puberty, biochemical parameters of puberty onset [Luteinizing hormone (LH), 17-β-estradiol, testosterone], and bone age progression were evaluated., Results: Pubertal onset and pubarche occurred significantly earlier in children with SRS than in SGA (p 0.03 and p 0.001, respectively) and clinical signs of puberty onset occurred earlier in mUPD7 than in 11p15LOM group (p 0.003). Five SRS children experienced central precocious puberty and LH, 17-β-estradiol, testosterone were detected earlier in SRS than in SGA (p 0.01; p 0.0001). Bone age delay in SRS children was followed by rapid advancement; the delta between bone age and chronological age in SRS group became significantly higher than in SGA group at the age of 9-11 years (p 0.007). 11p15LOM patients were underweight at the age of 5 years and showed a progressive normalization of BMI that was significantly higher than in mUPD7 (p 0.04) and SGA groups (p 0.03) at puberty onset., Conclusion: Timing of puberty is affected in SRS and occurred earlier in mUPD7 compared to 11p15LOM. The impact of early puberty on adult height and metabolic status deserves long-term evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Patti, Malerba, Calevo, Schiavone, Scaglione, Casalini, Russo, Fava, Bassi, Napoli, Allegri, D’Annunzio, Gastaldi, Maghnie and Di Iorgi.)

Skeletal disorders, including both isolated and syndromic brachydactyly type E, derive from genetic defects affecting the fine tuning of the network of pathways involved in skeletogenesis and growth-plate development. Alterations of different genes of this network may result in overlapping phenotypes, as exemplified by disorders due to the impairment of the parathyroid hormone/parathyroid hormone-related protein pathway, and obtaining a correct diagnosis is sometimes challenging without a genetic confirmation. Five patients with Albright's hereditary osteodystrophy (AHO)-like skeletal malformations without a clear clinical diagnosis were analyzed by whole-exome sequencing (WES) and novel potentially pathogenic variants in parathyroid hormone like hormone (PTHLH) (BDE with short stature [BDE2]) and TRPS1 (tricho-rhino-phalangeal syndrome [TRPS]) were discovered. The pathogenic impact of these variants was confirmed by in vitro functional studies. This study expands the spectrum of genetic defects associated with BDE2 and TRPS and demonstrates the pathogenicity of TRPS1 missense variants located outside both the nuclear localization signal and the GATA ((A/T)GATA(A/G)-binding zinc-containing domain) and Ikaros-like binding domains. Unfortunately, we could not find distinctive phenotypic features that might have led to an earlier clinical diagnosis, further highlighting the high degree of overlap among skeletal syndromes associated with brachydactyly and AHO-like features, and the need for a close interdisciplinary workout in these rare patients. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

We report the case of a 77-year-old man with Parkinson's disease (PD) who experimented for the first time gout crisis after the initiation of levodopa. Levodopa was withdrawn, and colchicine and allopurinol were initiated to treat the gout crisis. Because of PD progression, levodopa was reintroduced, and the patient presented relapse of gout flare. To further explore the association between gout and levodopa, we extracted and synthetized all Individual Case Safety Reports of gout associated with levodopa in the World Health Organization pharmacovigilance database, VigiBase ® , up to April 2021. 43 cases of gout were reported in VigiBase ® with drugs from N04BA ATC class. Levodopa was suspected in fifteen cases among which improvement was noticed in six cases (two after levodopa withdrawal, two despite treatment continuation, and two cases lacking details about action taken with levodopa); three cases did not recover; in the remaining six cases, evolution was not known. "Hyperuricemia" was not mentioned in the Summary of Product Characteristics of medicine containing levodopa; however, "abnormality biologics test with uric acid" was mentioned. Despite few cases of recovery after reduced doses of levodopa, the above-described case of positive reintroduction was an argument in favor of the role of levodopa in gout flare. This study highlights a potential association between levodopa and gout through an analysis of the cases reported in the WHO pharmacovigilance database., (© 2021 Société Française de Pharmacologie et de Thérapeutique.)