Need for integration of hepatitis C (HCV) services in community-based settings for people who inject drugs: results from a global values and preferences survey.

BACKGROUND: To inform the development of updated World Health Organization (WHO) guidelines on simplified service delivery for HCV infection, a global survey was undertaken among people affected or infected by HCV. The objective of this analysis is to identify specific needs and preferences among people who inject drugs. METHODS: A multi-country, anonymous, self-administered online survey conducted in 2021 was developed by Coalition PLUS and the World Hepatitis Alliance in partnership with the WHO. Preferences for test and treat locations and simplifying HCV care were collected among people affected or infected by HCV. Chi-square tests were used to compare respondents who identified with current or former injection drug users through identification with key population to other respondents who did not identify with this key population. RESULTS: Among 202 respondents, 62 (30.7%) identified with current/former injection drug users. Compared to other respondents, they were: older [median (IQR): 48 (36-57) vs. 39 (31-51) years, p = 0.003]; more likely to have been tested for HCV (90.2% vs. 64.3%, p = 0.001); more likely to prefer testing in a community-based centre (CBC) (55.4% vs. 33.3%, p = 0.005); or in a support centres for people who use drugs (SCPUD)(50.0% vs. 9.8%, p < 0.001). The most important considerations regarding testing locations among people identified with current/former injection drug users (compared to the other respondents) were: non-judgemental atmosphere (p < 0.001), anonymity (p = 0.018) and community worker (CW) presence (p < 0.001). People identified with current/former injection drug users were more likely to prefer to receive HCV treatment in a CBC (63.0% vs. 44.8%, p = 0.028) or in a SCPUD (46.3% vs. 9.5%, p < 0.001), compared to the other respondents. The most important considerations regarding treatment locations among people identified with current/former injection drug users were the non-stigmatising/non-judgemental approach at the site (p < 0.001) and the presence of community-friendly medical personnel or CW (p = 0.016 and 0.002), compared to the other respondents. CONCLUSION: The preferences of people identified with current/former injection drug users indicated specific needs concerning HCV services. Integration of HCV services in community-based risk reduction centres may be an important element in the development of adapted services to increase uptake and retention in HCV care among this population.

Italian consensus recommendations for a biomarker-based aetiological diagnosis in mild cognitive impairment patients.

BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.

Vitamin D receptor polymorphisms and 25-hydroxyvitamin D in a group of Sicilian multiple sclerosis patients.

Multiple sclerosis (MS) is an auto-immune disease whose etiology remains controversial. Both genetic and environmental factors are thought to be involved in the risk of developing the disease. The purpose of our study was to assess the association of Vitamin D receptor (VDR) polymorphisms with MS and to investigate the interaction of these polymorphisms with vitamin D levels. A total of 179 Sicilian subjects, including 104 MS patients and 75 healthy controls, were studied. The most common VDR polymorphisms (Fok-I, Bsm-I, Taq-I and Apa-I) were genotyped by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analyses in both groups and serum 25-hydroxyvitamin D [25(OH)D] levels were determined in MS patients by high-performance liquid chromatography (HPLC). The distribution of genotype and allele frequencies of the four VDR polymorphisms did not differ significantly between MS patients and healthy controls, and were unrelated to the forms and the course of MS. Low serum levels of 25(OH)D were observed in MS patients but no association was observed between VDR and 25(OH)D levels except for Fok-I. Moreover, MS patients with FF and Ff genotype had a significantly lower serum levels of 25(OH)D compared with ff carriers (P < 0.05 FF vs Ff and Ff vs ff). Our findings showed no association between VDR polymorphisms and risk of MS. Interestingly, F allele could confer a genetic predisposition to lower 25(OH)D levels.

Arterial stiffness indexes and serum cytokine levels in seronegative spondyloarthritis: relationships between stiffness markers and metabolic and immunoinflammatory variables.

OBJECTIVE: The aim of this study was to investigate the relationship between immunoinflammatory markers and indexes of arterial stiffness in patients with seronegative spondyloarthritis (SpA). METHOD: We enrolled consecutive patients with inflammatory seronegative SpA referred to a rheumatology outpatient clinic. Control subjects were patients admitted in the same period for any cause other than chronic inflammatory disease or acute cardiovascular and cerebrovascular events. Carotid-femoral pulse wave velocity (PWV) was measured and the aortic pressure waveform was used to calculate the augmentation index (Aix). We also evaluated plasma levels of C-reactive protein (CRP), interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, and interleukin (IL)-6 as markers of immunoinflammatory activation. RESULTS: This study enrolled 53 patients with SpA and 55 control subjects. After adjustment for blood glucose, cholesterol, and triglyceride levels, and systolic (SBP) and diastolic blood pressure (DBP), patients with seronegative SpA showed higher mean PWV and Aix compared to controls. Moreover, in patients with seronegative SpA, we observed higher mean plasma levels of IL-6, IL-1ß, and TNF-α in subjects with mean PWV > 8 m/s in comparison with those with PWV < 8 m/s. Multivariate analysis revealed a significant association between PWV > 8 m/s and male gender, age, diabetes, hypertension, low density lipoprotein cholesterol (LDL-C) > 120 mg/dL, total cholesterol (TC) > 200 mg/dL, coronary artery disease (CAD), microalbuminuria, carotid plaque, and plasma levels of IL-6, IL-1ß, and TNF-α. CONCLUSIONS: These findings emphasize the role of inflammatory variables and metabolic factors in indexes of high arterial stiffness. Thus, an inflammatory-metabolic background may influence the pathogenesis of increased arterial stiffness in seronegative inflammatory arthritis.

Características clínicas y etiología de la ginecomastia en pacientes en edad prepuberal / Clinical features and etiology of gynecomastia in patients at prepubertal age

La ginecomastia es la proliferación benigna del tejido glandular mamario del varón, generalmente aparece en ciertos periodos de la vida como la época neonatal, puberal o senil, siendo la expresión de cierto disbalance en la acción de estrógenos y andrógenos en la glándula mamaria. Es poco frecuente durante la prepubertad y se debe investigar exhaustivamente el origen de la misma. Objetivo: evaluar las características clínicas y poder definir la etiología en un grupo de pacientes con ginecomastia prepuberal, Materiales y métodos: es un estudio retrospectivo, descriptivo y multicéntrico. Se recolectaron datos de antecedentes familiares, personales, examen físico, laboratorio, evolución, conducta terapéutica y se determinaron las posibles etiologías. Resultados: Fueron evaluados 53 pacientes con ginecomastia, con edad media de 8,4 años (0,88-13,72 años), se encontró mayor prevalencia en niños mayores de 7 años (79,2 %). La presentación bilateral fue la más frecuente en el 73,5 %, 17 (32 %) presentaron obesidad, siendo en 7 (13,7 %) severa (IMC ≥ 3 SDS). En 34 pacientes (64,1 %) no se encontró la etiología; en 12 pacientes (23,5 %) se constató fuente exógena de estrógeno; 2 pacientes con exceso de aromatasa; 1 con neurofibromatosis tipo I y glíoma del nervio óptico; 1 niño con tumor suprarrenal izquierdo productor de estrógenos y 1 paciente con síndrome de Peutz-Jeghers. Conclusión: La ginecomastia prepuberal es poco común, en esta población el mayor porcentaje fue idiopática o por exposición a estrógenos exógenos, pero es una señal de alarma que obliga a descartar la presencia de un trastorno endocrinológico importante.

Gynecomastia is the benign proliferation of male breast glandular tissue. The occurrence of gynecomastia at prepubertal ages is very uncommon and can be a sign of severe endocrine or systemic disease. The main underlying mechanism for the development of gynecomastia appears to be the imbalance between estrogen and androgen action. Objective: to assess clinical characteristics, etiology and course of prepubertal gynecomastia in a group of patients regularly followed at the endocrinology clinic. We performed a retrospective, descriptive, multicenter study. Materials and methods: data on family history, past history of the disease, physical examination, and clinical course were collected. Results: 53 prepubertal patients were included. Median age at presentation was 8.4 years (0.88-13.72 years). An increased prevalence was observed in children > 7 years (79.2 %). Bilateral gynecomastia was the most common form of presentation, (73.5 %). Seventeen patients (32 %) were obese, 7 (13.7 %) with a BMI above 3 SDS. In 34 patients (64.1 %) the etiology of gynecomastia could not be identified (idiopathic). In 12 patients (23.5 %) estrogen exposure was detected; 2 patients suffered from aromatase excess syndrome, 1 had neurofibromatosis type I and optic glioma, 1 had a feminizing adrenocortical tumor and 1 had Peutz-Jeghers syndrome. Conclusion: Prepubertal gynecomastia is rare. In this cohort of 53 children, the most common etiologies were idiopathic or exogenous estrogens exposure. Although gynecomastia may be due to benign causes, in the majority of patients evaluations should be performed to rule out a severe underlying systemic or endocrine disease.

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C.

Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 µg/L vs 12.5 ± 5.8 µg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.

Displasia septo-optica. Evaluación clínica, endocrinológica y neuro-radiológica. Seguimiento de 46 pacientes pediátricos / Septo-optic dysplasia. Clinical, endocrinological, and neuroradiological evaluation. Follow-up of 46 pediatric patients

La displasia septo-óptica (DSO) es una condición rara y altamente heterogénea, definida por la combinación de hipoplasia del nervio óptico (HNO), malformaciones cerebrales de la línea media, tales como aplasia/hipoplasia de septum pellucidum y cuerpo calloso, e insuficiencia hipotálamo-hipofisaria de grado variable. Se realizó un trabajo que tuvo como objetivo caracterizar la población de pacientes con diagnóstico de DSO seguidos en nuestro Hospital durante 7 años. Se incluyeron 46 pacientes (18 mujeres) que fueron divididos en 2 grupos, según tuviesen o no insuficiencia hipotálamo-hipofisaria (IHH). El 58.7% (n=27) presentó IHH de algún tipo, mientras que el 41.3% (n=19) no la presentó. En aquellos 19 pacientes con IHH se diagnosticaron deficiencia de GH y TSH (85.1%) y de ACTH (48.1%). La longitud corporal (mediana) del grupo con IHH fue más baja (p = 0,01) que la del grupo sin IHH, a pesar de que la edad fue menor a 2 años en todos los casos. Los pacientes fueron seguidos 1,3-8,3 años. Se observaron incidencias similares de agenesia del cuerpo calloso, del septum pellucidum, y ventriculomegalia, pero las alteraciones del desarrollo cortical se observaron con mayor frecuencia en los pacientes sin IHH. La ictericia neonatal, convulsiones y/o hipoglucemia, y micropene en neonatos y lactantes con DSO se presentaron en el subgrupo con IHH. El 58,7% de los pacientes con DSO presentaron algún grado de insuficiencia hipotálamo-hipofisaria. En la mayoría de los casos el diagnóstico de IHH no se realizó en el momento de aparición de los síntomas, sino más tardíamente en su seguimiento. En el 45% de los pacientes se evaluaron alteraciones radiológicas del SNC, específicamente en la región hipofisaria. Una fracción importante de las deficiencias de TSH/T4 (36,4%), GH (50%) y ACTH (23%) aparecieron mas tardíamente en el curso de la evolución. En 10 niños con déficit de hormona de crecimiento (2 tests farmacológicos sin respuesta) se realizó el tratamiento sustitutivo con rhGH (durante un periodo de 4±3 años), observándose una mejoría promedio de + 1,5 SDS en la talla de estos pacientes. En conclusión, la hipoplasia neonatal de nervios ópticos, asociada o no a ictericia e hipoglucemia, debe ser un signo de alarma para el diagnóstico de DSO, con riesgo de insuficiencia suprarrenal, shock y muerte, y puede requerir, por lo tanto, urgente tratamiento. Las deficiencias pueden aparecer en el curso de la evolución, a pesar del carácter congénito de la anomalía. Finalmente, se deben sustituir las deficiencias hormonales y tener presente que el tratamiento con rhGH puede mejorar la talla final en estos pacientes (AU)

Septo-optic dysplasia (SOD) is a rare and highly heterogeneous condition consisting of a combination of optic nerve hypoplasia (ONH), midline brain abnormalities, such as aplasia/hypoplasia of the septum pellucidum (ASP) and corpus callosum; and variable degree of hypoyalamo-pituitary insufficiency. The aim of this study was to characterize a population of SOD patients diagnosed and followed at the Garrahan Pediatric Hospital, from 1989 to 2006. We included 46 patients (18 females), that were divided into two groups according to the presence or absence of hypothalamic-pituitary insufficiency (IHH). Fifty nine% of SOD patients presented with IHH. GH and TSH deficiencies were diagnosed in 85.1% of IHH patients, while ACTH deficiency was found in 48.1%. Height (median) for the IHH group was shorter (p = 0,01) than for the group without IHH. Patients were followed for 1.3-8.3 years. Similar incidence of corpus callosum and/or septum pellucidum agenesis and ventriculomegaly were found in the two groups, but we observed more association with cortical developmental disorders in patients without IHH. In newborns, the association of ophthalmologic disorders and jaundice, seizures and/or hypoglycemia and micropene should frequently lead to the diagnosis of SOD and IHH. While 58,7% of DSO patients presented with hypothalamic-pituitary deficiency, only 45% of them showed sellar radiological abnormalities. Although SOD is a congenital disease, hormonal deficiencies may appear during follow-up. In 10 children with SOD and GH deficiency, rhGh treatment (for 4±3 years) improved height in 1.5 SDSs. In conclusion: in newborns with nerve optic hypoplasia, associated or not with jaundice, seizures and hypoglycaemia, the diagnosis of SOD and IHH should be considered. Treatment could be an emergency need because of risk of adrenal insufficiency and hypoglycemia (AU)

Tumores del sistema nervioso central de localización selar y supraselar. Alteraciones neuro-oftalmológicas y de la función endocrina al diagnóstico / Sellar and suprasellar central nervous system tumors. Neuro-ophthalmological and endocrine function impairment at diagnosis

Los tumores (Tu) del SNC constituyen la segunda enfermedad oncológica en edad pediátrica, con una incidencia referida aproximada que oscila entre el 10 y 15%. En 309 pacientes con tumores selares y supraselares, seguidos durante 15 años, se evaluó en función de los distintos oncotipos tumorales, síntomas iniciales y alteraciones endocrinológicas previas al inicio del tratamiento. De ellos, 227 pacientes presentaron el tumor a edad prepuberal. Los oncotipos tumorales más frecuentes fueron craneofaringioma (CRA), glioma (GLIA) y tumor de células germinales (GERM). También, se encontró una mayor incidencia de presentación en varones. En edad puberal (n:92), el oncotipo tumoral más frecuente fue adenoma hipofisario (ADENO), seguido de GLIA y CRA. En este ultimo oncotipo tumoral, y, a diferencia del grupo prepuberal, su incidencia fue significativamente mayor en niñas. Aproximadamente 90% de los pacientes tuvieron anormalidades neuro-oftalmológicas (hipertensión craneal, dolores de cabeza, vómitos y pérdida progresiva de la visión) como uno de los signos y/o síntomas iniciales. Alteraciones clínicas endocrinológicas como baja talla, velocidad de crecimiento anormal, diabetes insípida y alteraciones del tempo puberal son frecuentes en estos pacientes y están habitualmente asociadas con las alteraciones clínico-neuro-oftalmológicas como las ya mencionadas. No obstante, la mayoría de los tumores del SNC localizados en la línea media suelen ser diagnosticados por manifestaciones neuro-oftalmológicas. Los resultados del estudio muestran alteración de la función endócrina al diagnóstico del Tu. Se concluye que en todo paciente con crecimiento lento o baja talla, así como también signos clínicos que orienten a un diagnóstico de pubertad precoz y/o retardada, el pediatra debe incluir dentro de los diagnósticos diferenciales, el diagnóstico del tumor selar o supraselar. La morbilidad aumenta frecuentemente luego de la cirugía (AU)

During the last 15 years, 309 patients with tumors of the sellar and suprasellar areas of CNS were followed in our Hospital (Endocrine Service). Tumor oncotype, initial symptoms and endocrine disturbances before any treatment was started are presented. In 227 patients, the tumor was diagnosed at prepubertal age. In this group, the most frequent tumoral oncotypes were craniopharyngioma (CRA), glial tumors (GLIA) and germ cells tumors (GERM). The incidence was higher in boys. At pubertal age (n:92), the most frequent tumoral oncotype was pituitary adenoma (ADENO), followed by GLIA and CRA. In the latter, and different from the prepubertal group, the incidence was significantly higher in girls. Approximately 90% of patients had neuro-ophtalmological abnormalities (cranial hypertension, headaches, vomits, and progressive loss of vision) as one of the initial signs and/or symptoms. Clinical endocrine disorders, such as short stature, low growth velocity, diabetes insipidus, and alterations in pubertal "tempo" are frequent in these patients and are often associated with the neuro-ophtalmological abnormalities mentioned above. This clinical symptomatology has to alert the medical team to discard the presence of a CNS tumor at the sellar and/or suprasellar level. We conclude that tumors of the SNC localized in the midline, have potential capacity to provoke abnormalities in endocrine function. Morbidity is often increased after surgery (AU)

Talla final en pacientes transplantados renales bajo tratamiento con hormona de crecimiento / Final height in renal transplant patients after growth hormone treatment

El retardo de crecimiento es un importante problema clínico aun no resuelto ni correctamente manejado en niños con insuficiencia renal crónica (IRC). La optimización de todos los parámetros metabólicos y nutricionales no siempre lleva a una mejoría del crecimiento en estos pacientes. Desde hace aproximadamente 20 años se utiliza el tratamiento con rhGH para mejorar la talla en este grupo de niños. La bibliografía internacional muestra mejoría de la velocidad de crecimiento en estos pacientes sin embargo la experiencia publicada en la talla final (TF) alcanzada por los mismos es escasa. Los objetivos de este estudio fueron:1) evaluar la talla final alcanzada por pacientes transplantados renales(TxR) que recibieron tratamiento con rhGH (GrGH) comparándolos con un grupo control (GrC) con similares características clínicas, 2) evaluar los factores predictores de la TF, y 3) la repercusión de dicho tratamiento en la función renal. La TF en el GrGH fue significativamente mayor que la TF del GrC (-1.96 ± 1.13 vs -3.48 ± 1.19 SDS respectivamente, p <0.05). La talla (SDS) al inicio del tratamiento con rhGH fue la única variable significativa para predecir la respuesta al tratamiento (p= 0.001). Se observó una disminución significativa ClCr final en ambos grupos (GrGH: 76 ± 18 vs 66 ± 14 ml/min/m2 sup p<0.05; GrC: 72 ± 19 vs 56 ± 9 ml/min/m2 sup, p<0.05) lo que sugiere una caída similar del filtrado glomerular en ambos grupos independiente del tratamiento. Conclusión: Nuestros hallazgos permiten confirmar que el tratamiento con rhGH es efectivo para mejorar la talla final en pacientes TxR sin afectar la función renal (AU)

Growth retardation is a common and significant clinical problem that is not adequately managed in children with chronic renal disease. Despite optimization of metabolic parameters the growth of this patients not always amelioreted. About 20 years ago rhGH treatment became to be used for this group of children to optimization final height.The international experience show that rhGH treatment improve growth velocity but the results about final heigth are scarse. The aims of our trial were: 1) to evaluate final height in renal transplant patients treated with rhGH (n=23) comparing with a control group not treated with rhGH (n=14) with similar characteristics, 2) to evaluate the effect of rhGH on creatinine clearance,3) to establish predictive variables for final height. Final Heigth was significantly greater in treated group vs control group (-1.9±1.1 vs -3.5±1.2, p<0.05). Initial height was the only significant variable to predict final height (p=0.001). We described a significantly decrease of creatinine clearence in both groups during follow up (GH Group 76±9 vs 66±14 ml/min/m2 sup, p<0.05 and Control Group 72.5±19 vs 56±9 ml/min/m2 sup, p= p<0.05).This suggest a similar decrese of creatinine clearence in both groups. Conclution: Our data confirm that rhGH treatment was effective in improving final height in renal transplant patients and did not decline allograft function (AU)

Evaluación de la talla final y sobrevida libre de eventos en pacientes sobrevivientes de meduloblastoma con deficiencia de hormona de crecimiento, tratados o no con hormona de crecimiento biosintética recombinante humana en la niñez. Comparación con pacientes con craneofaringioma tratados con rhGH / Evaluation of final height and event-free survival in medulloblastoma patients with growth hormone deficiency with and without biosynthetic recombinant human growth hormone treatment in childhood

Introduccion: La deficiencia de GH (DGH) y la radioterapia espinal (RE) han sido implicadas en la etiología de la talla adulta (TA) baja en los sobrevivientes de meduloblastoma en la niñez. Sin embargo la dinámica del crecimiento luego del diagnóstico tumoral y la efectividad de la Hormona de crecimiento biosintética recombinante humana (rhGH) sobre la TA en comparación con sobrevivientes no tratados con rhGH no han sido reportadas. Objetivo. Evaluación de la talla (T) SDS (SDST) desde el diagnóstico del meduloblastoma y el efecto de la rhGH en pacientes con DGH comparando con pacientes no tratados con rhGH y con pacientes con craniofaringioma y DGH, tratados con rhGH. Analizar si había alguna diferencia en la sobrevida libre de eventos en los pacientes con meduloblastoma al ser tratados con rhGH. Material Clínico y Métodos. Catorce pacientes con meduloblastoma recibieron rhGH hasta la TA, grupo meduloblastoma tratado con GH (GrMGH). Diecinueve pacientes rechazaron la terapia con rhGH, grupo meduloblastoma control (GrMC). Se midieron la talla parada (T) y la talla sentada (Tsent). Ocho pacientes con craneofaringioma recibieron rhGH hasta la TA (GrCra). Se realizó seguimiento de 72 pacientes con meduloblastoma, 20 con tratamiento con rhGH. Resultados. En GrMGH, la media±DS SDST disminuyó de 0.09±0.63 al diagnóstico del tumor a -1.38±0.91 al diagnóstico del DGH, y a -1.90±0.72 al comienzo de rhGH, p<0.01, pero se mantuvo sin cambios durante el tratamiento con rhGH (TA -2.12±0.55). En GrMC la SDST (-0.25±0.88) no fue diferente de GrMGH al diagnóstico del tumor, pero fue -3.40±0.88 a la TA, significativamente menor que en GrMGH, p=0.001. La Tsent SDS a la TA (-4.56±0.82) fue significativamente menor que al comienzo de rhGH (-2.86±0.75), p=0.003, y no fue diferente de GrMC (-4.85±1.77). El GrCra mostró la mayor ganancia de talla (GT = TA-SDSTinicial), p< 0.007, y la menor pérdida de talla (PT= Tblanco - TA), p < 0.0001. Conclusión. El tratamiento con rhGH mejora la TA en sobrevivientes de meduloblastoma en la niñez con DGH, pero no el crecimiento espinal. Las características del crecimiento y la respuesta a rhGH son diferentes en GrMGH y en GrCra, mientras que el primer grupo sólo pudo mantener la talla relativa, el segundo mostró una franca recuperación del crecimiento. Además no hubo diferencias en la sobrevida libre de eventos en los pacientes con meduloblastoma con y sin tratamiento con rhGH (AU)

Background. GH deficiency (GHD) and spine irradiation (SI) have been implicated in the mechanism of reduced adult height (AH) in childhood survivors of medulloblastoma. However, growth dynamics after tumor diagnosis and the effectiveness of (rhGH) Recombinant human Growth Hormone on AH in comparison with rhGH-untreated survivors has not been reported. Aim. Follow up of height (H) SDS (HSDS) after diagnosis of meduloblastoma, and the effect of rhGH in GHD meduloblastoma patients. Comparison with GH-untreated GHD meduloblastoma patients and with GHD craniopharyngioma patients treated with rhGH. To evaluate event free survival in medulloblastoma patiens treated with rhGH. Clinical Material and Methods. Fourteen survivors of medulloblastoma received rhGH treatment until AH, Medulloblastoma GH-treated group (MGHGr). Nineteen patients refused rhGH therapy, GH-untreated Control Medulloblastoma Group, (MCGr). Standing H and sitting H (SitH) were measured. Eight patients with craniopharyngioma received rhGH treatment until AH (CraGr). 72 patients with medulloblastoma were followed up, 20 with rhGH. Results. In MGHGr, mean±SD HSDS decreased from 0.09±0.63 at tumor diagnosis to -1.38±0.91 at diagnosis of GHD, and to -1.90±0.72 at the onset of rhGH, p<0.01, but it remained unchanged during rhGH (AH -2.12±0.55). MCGr HSDS (- 0.25±0.88) was not different from MGHGr at tumor diagnosis, but it was -3.40 ± 0.88 at AH, significantly lower than in MGHGr, p=0.001. SitH SDS at AH (-4.56±0.82) was significantly lower than at the onset of rhGH (-2.86±0.75), p=0.003, and it was not different from MCGr (-4.85 ± 1.77). CraGr showed the highest height SDS gain (HG = FH ­ startHSDS), p<0.007, and the lowest height lost (HL = targetH - AH), p< 0.0001. Conclusions. rhGH treatment improves AH in GH-deficient childhood medulloblastoma survivors but not spinal growth. Growth pattern and response to rhGH differed in MGHGr and CraGR, while the former just could maintain height SDS under treatment, the latter showed a clear catch up growth. There wasn't any difference in the event free survival in medulloblastoma patients with or without rhGH (AU)

Effectiveness of rhGH treatment on adult height in GH-deficient childhood survivors of medulloblastoma.

BACKGROUND: GH deficiency (GHD) and spine irradiation (SI) have been implicated in the mechanism of reduced adult height (AH) in childhood survivors of medulloblastoma. However, growth dynamics after tumor diagnosis and the effectiveness of rhGH on AH in comparison with rhGH-untreated survivors have not been reported. AIM: To follow height (H) SDS (HSDS) since tumor diagnosis and the effect of rhGH in GHD patients, comparing with GH-untreated GHD patients. METHODS: 14 patients received rhGH treatment until AH (medulloblastoma GH-treated group, MGHGr). 19 patients refused rhGH therapy (GH-untreated control medulloblastoma group, MCGr). Standing H and sitting H (SitH) were measured. RESULTS: In MGHGr, mean +/- SD HSDS decreased from 0.09 +/- 0.63 at tumor diagnosis to -1.38 +/- 0.91 at diagnosis of GHD, and to -1.90 +/- 0.72 at the onset of rhGH, p < 0.01, but it remained unchanged during rhGH (AH -2.12 +/- 0.55). MCGr HSDS (-0.25 +/- 0.88) was not different from MGHGr at tumor diagnosis, but it was -3.40 +/- 0.88 at AH, significantly lower than in MGHGr, p = 0.001. SitH SDS at AH (-4.56 +/- 0.82) was significantly lower than at the onset of rhGH (-2.86 +/- 0.75), p = 0.003, and it was not different from MCGr (-4.85 +/- 1.77). CONCLUSIONS: rhGH treatment improves AH in GH-deficient childhood medulloblastoma survivors but not spinal growth.

Fetuin-A and CD40 L plasma levels in acute ischemic stroke: differences in relation to TOAST subtype and correlation with clinical and laboratory variables.

INTRODUCTION: Accumulating evidence suggests that inflammation plays an important role in the acute phase of ischemic stroke. CD40 L is a well recognized atherosclerotic inflammatory marker, whereas recent evidence suggests a pro-inflammatory role of Fetuin-A. To analyze the role of an inflammatory marker such as CD40 L and of a candidate pro-inflammatory marker such as Fetuin-A in acute stroke we evaluated their serum levels in subjects with acute ischemic stroke and their possible association with other laboratory and clinical variables. MATERIALS AND METHODS: We enrolled 107 consecutive patients with a diagnosis of acute ischemic stroke admitted to the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and 102 hospitalized control patients without a diagnosis of acute ischemic stroke. RESULTS: Patients with acute ischemic stroke in comparison to control subjects without acute ischemic stroke had significantly higher CD40 L levels and Fetuin-A serum levels. No significant differences in plasma CD40 L or Fetuin-A levels among different TOAST groups were detected. At intragroup (intra-TOAST-subtype) correlation analysis, among subjects classified as lacunar, CD40 L plasma levels were positively correlated with LDL-cholesterol and with diabetes, whereas Fetuin-A was significantly (positively) correlated with hypertension and white blood cell count. Among subjects with LAAS subtype, CD40 L levels were positively correlated with triglyceride plasma levels and Fetuin-A, whereas Fetuin-A levels were positively correlated with LDL-cholesterol. DISCUSSION: Our findings suggest a pro-inflammatory role of Fetuin-A and CD40 L in acute stroke setting. Whether this role should be construed as direct or as a simple expression of a general inflammatory activation will be up to future studies to clarify.

Elevated cerebrospinal fluid and plasma homocysteine levels in ALS.

BACKGROUND: High cerebrospinal fluid (CSF) and plasma levels of homocysteine (HC) have been reported in certain neurodegenerative disorders, such as Alzheimer's, Parkinson's diseases and, recently, amyotrophic lateral sclerosis (ALS). OBJECTIVES: To assay the CSF and plasma levels of HC in ALS patients and controls, and to evaluate the relationship between HC levels and clinical variables of the disease. METHODS: Cerebrospinal fluid from sixty-nine (M/F 1.87) and plasma from sixty-five ALS patients (M/F 1.83) were taken and stored at -80 degrees C until use. Controls (CSF = 55; plasma = 67) were patients admitted to our hospital for neurological disorders with no known relationship to HC changes. CSF and plasma from ALS patients and controls were obtained as a necessary step of the diagnostic workup. HC levels in CSF and plasma were assayed using a high performance liquid chromatograph (HPLC) and a fluorimeter detector. RESULTS: The median level of total HC in the CSF of ALS patients was 0.46( )microM, significantly higher than that of the controls (0.24 microM, +91.6%, P < 0.001). A similar trend was observed when HC was assayed in plasma (ALS, 12.4 microM vs. controls, 7.26 microM, +70.8%, P < 0.001). The CSF and plasma HC levels showed no relationship with the disease progression, age at onset, and the site of onset. CONCLUSIONS: Homocysteine is a biochemical marker in ALS, and it might be related to the pathophysiology of the disease.

Meduloblastoma: nuestra experiencia / Medulloblastoma: our experience

Los tumores del Sistema Nervioso Central, ocupan el segundo lugar en frecuencia dentro de la oncología paediátrica, solo superados en números por las Leucemias Agudas. Estos son una población heterogénea representada por tumores considerados benignos o malignos; dentro de los clasificados como malignos el más frecuentees el meduloblastoma. Su frecuencia está representada en 10 de nuestros registros tumorales neuropatológicos. Objetivo: presentar resultados obtenidos en un estudio propectivo de tratamiento para niños con meduloblastoma, ingresados en el Hospital Garrahan desde junio de 1991 a diciembre de 2005. Material y Metodos: Las estrategias terapéuticas fueron distintas según el grupo etario, se definieron 2 grupos según la edad: mayores y menores de 36 meses. A su vez cada grupo se dividio en grupos de riesgo estándar (RE) y de riesgo alto (RA) según tuvieran o no diseminación metastásica al diagnóstico. La diferencia fundamental en la terapéutica fue el uso de radioterapia seguida de quimioterapia adyuvante versus la quimioterapia solamente para los niños mayores y menores de 36 m respectivamente después de la cirugía. Resultados: ingresaron un total de 203 pacientes: 170 mayores y 33 menores de 36 m de edad, fueron evaluados 116 niños mayores; 74 de RE y 42 de RA y 24 niños menores; 18 y 6 de RE y RA respectivamente. La SLE /SG alcanza en los grupos de más de 36 m fue de 5 años 75 / 75 para el RE y de 44 y 51 para el RA a 5 años. En los menores de 36 meses los resultados fueron muy pobres, con una SLEa 5 y 10 años de 39 y 19 para el grupo de RE y de solo 16 a 1año pra el grupo RA. Se analizó el patrón de recaída de cada subgrupo y según ello se planteó la orientación de una nueva conducta terapéutica.

Maternal hyperphenylalaninemia syndrome: neuropsychological evaluation of four subjects during childhood and adolescence.

Maternal hyperphenylalanemia during pregnancy may induce a severe embryopathy characterized by microcephaly, mental retardation, facial dysmorphy and congenital heart defects. Four subjects, two pairs of sibs, with maternal hyperphenylalaninemia syndrome were included in this study and their neuropsychological performances were assessed. Maternal levels of hyperphenylalaninemia were similar in both mothers, one of them had not been diagnosed with the condition until her two children were examined at the ages of 10 and 6 years. A severe cognitive deficit was detected in all 4 subjects, with a typical profile of impaired perceptive abilities, behavioural disturbances, motor difficulties and poor familiar integration.