Il craniofaringioma nel bambino e nell'adolescente. Luci ed ombre durante il follow-up

Introduction. Craniopharyngioma (CF) is a malformation of the hypothalamicpituitary region and it is the most common nonglial cerebral tumor in children with an high overall survival rate. In some case severe endocrinologic and metabolic sequelae may occur during follow up. 50% of patients (pts), in particular those with radical removal of suprasellar lesions, develop intractable hyperphagia and morbid obesity, with dyslypidemia and high cardiovascular risk. We studied the auxological and metabolic features of a series of 29 patients (18 males) treated at a mean age of 7,6 years, followed up in our Centre from 1973 to 2008 with a mean follow up of 8,3 years. Patients features at the onset. 62% of pts showed as first symptoms of disease visual impairment and neurological disturbancies (headache); 34% growth arrest; 24% signs of raised intracranial pressure and 7% diabetes insipidus. Diagnosis. Diagnosis of CF was reached finally by TC or MRI scans which showed endo-suprasellar lesion in 23 cases and endosellar tumour in 6 cases. Treatment and outcome. 25/29 pts underwent surgical removal of CF (19 by transcranial approach and 6 by endoscopic surgery); 4 pts underwent stereotactic surgery as first line therapy. 3 pts underwent local irradiation with yttrium-90, 5 pts post surgery radiotherapy. 45% of pts needed more than one treatment procedure. Results. After CF treatment all patients suffered from 3 or more pituitary hormone deficiencies and diabetes insipidus. They underwent promptly substitutive therapy with corticosteroids, l-thyroxine and desmopressin. In 28/29 pts we found growth hormone (GH) deficiency. 20/28 pts started GH substitutive therapy and 15 pts reached final height(FH) near target height(TH). 8 pts were not GH treated for good growth velocity, even without GH, or for tumour residual. They reached in 2 cases FH over TH showing the already known phenomenon of growth without GH. 38% of patients showed BMI SDS >2 SDS at last assessment, in particular pts not GH treated (BMI 2,5 SDS) are more obese than GH treated (BMI 1,2 SDS). Lipid panel of 16 examined pts showed significative differencies among GH treated (9 pts) and not treated (7 pts) with better profile in GH treated ones for Total Cholesterol/C-HDL and C-LDL/C-HDL. We examined intima media thickness of common carotid arteries in 11 pts. 3/4 not GH treated pts showed ultrasonographic abnormalities: calcifications in 2 and plaque in 1 case. Of them 1 pt was only 12,6 years old and already showed hypothalamic obesity with hyperphagia, high HOMA index and dyslipidemia. In the GH treated group (7) we found calcifications in 1 case and a plaque in another one. GH therapy was started in the young pt with carotid calcifications, with good improvement within 6 months of treatment. 5/29 pts showed hypothalamic obesity, related to hypothalamic damage (type of surgical treatment, endo-suprasellar primitive lesion, recurrences). 48% of patients recurred during follow up ( mean time from treatment: 3 years) and underwent, in some cases up to 4 transcranial surgical treatments. GH seems not to increase recurrence rate since 40% of GH treated recurred vs 66,6% of not GH treated pts. Discussion. Our data show the extereme difficulties that occur during follow up of craniopharyngioma treated patients. GH therapy should be offered to all patients even with good growth velocity after CF treatment, to avoid dislypidemia and reduce cardiovascular risk. The optimal therapy is not completely understood and whether gross tumor removal or partial surgery is the best option remains to be decided only on one patient tumour features and hypothalamic involvement. In conclusion the gold standard treatment of CF remains complete tumour removal, when feasible, or partial resection to preserve hypothalamic function in endosuprasellar large neoplasms.

Functional characterization of Streptococcus pyogenes pili

Group A Streptococcus is a Gram-positive human pathogen able to colonize both upper respiratory tract and skin. GAS is responsible for several acute diseases and autoimmune sequelae that account for half a million deaths worldwide every year (Cunningham et al., 2000). As other bacteria, GAS infections requires the capacity of the pathogen to adhere to host tissues and to form cell aggregates. The ability to persist in distinct host niches like the throat and the skin and to trigger infections is associated with the expression of different GAS virulence factors. GAS pili has been described as important virulence factors encoded by different FCT-operon regions. Based on this information, we decided to study the possible effect of environmental conditions that could regulate the pili expression. In this study we reported the influence of pH environment variations in biofilm formation for strains pertaining to a panel of different GAS FCT-types. The biofilm formation was promoted, excepted in the FCT-1 strains, by a changing in pH from physiological to acidic condition of growth in in vitro biofilm assay. By analyzing the possible association between biofilm formation and pH dependence, we have found that in FCT-2 and FCT-3 strains, the biofilm is promoted by pH reduction leading to an increase of pili expression. These data confirmed a direct link between pH dependent pilus expression and biofilm formation in GAS. As pili are a multi component structure we decided to investigate the functional role of one of its subunits, the AP-1 protein. AP-1 is highly conserved through the different FCT-types and suggests a possible essential role for the pili function. We focused our attention on the AP-1 protein encoded by the FCT-1 strains (M6). In particular this AP-1 protein contains the von Willebrand Factor A (VWFA) domain, which share an homology with the human VWFA domain that has been reported to be involved in adhesion process. We have demonstrated that the AP-1 protein binds to human epithelial cells by its VWFA domain, whereas the biofilm formation is mediated by the N-terminal region of AP-1 protein. Moreover, analyzing the importance of AP-1 in in vivo experiments we found a major capacity of tissue dissemination for the wild-type strain compared to the isogenic AP-1 deletion mutant. Pili have been also reported as potential vaccine candidates against Gram positive bacteria. For these reason we decided to investigate the relationship between cross reaction of sera raised against different GAS and GBS pilin subunits and the presence of a conserved Cna_B domain, in different pilin components. Our idea was to investigate if, using pilus conserved domains, a broad coverage vaccine against streptococcal infection could be possible.

Valutazione della funzione renale nei nati pretermine alla nascita e a medio termine

La nascita pretermine determina un’alterazione dei normali processi di maturazione dei vari organi ed apparati che durante la gravidanza fisiologica si completano durante le 38-40 settimane di vita intrauterina. Queste alterazioni sono alla base della mortalità e morbilità perinatale che condiziona la prognosi a breve termine di questa popolazione, ma possono determinare anche sequele a medio e lungo termine. E’ stato ampiamente documentato che la nefrogenesi si completa a 36 settimane di vita intrauterina e pertanto la nascita pretermine altera il decorso fisiologico di tale processo; a questa condizione di immaturità si sovrappongono i fattori patogeni che possono determinare danno renale acuto in epoca neonatale, a cui i pretermine sono in larga misura esposti. Queste condizioni conducono ad un rischio di alterazioni della funzione renale di entità variabile in età infantile ed adulta. Nel presente studio è stata studiata la funzione renale in 29 bambini di 2-4 anni di età, precedentemente sottoposti a valutazione della funzione renale alla nascita durante il ricovero in Terapia Intensiva Neonatale. I dati raccolti hanno mostrato la presenza di alterazioni maggiori (sindrome nefrosica, riduzione di eGFR) in un ridotto numero di soggetti e alterazioni minori ed isolate (proteinuria di lieve entità, riduzione del riassorbimento tubulare del fosforo, pressione arteriosa tra il 90° e il 99° percentile per sesso ed altezza). L’età di 2-4 anni, alla luce dei risultati ottenuti, può rappresentare un momento utile per effettuare una valutazione di screening di funzione renale in una popolazione a rischio come i pretermine, con lo scopo di individuare i soggetti che richiedano una presa in carico specialistica ed un follow-up a lungo termine.

Adulthood with Turner Syndrome: Quality of life, psychosocial adjustment and clinical management in 70 Italian women

Abstract Background: Turner syndrome (TS) is a chromosomal abnormality (total or partial absence of one of the sexual chromosomes in some or all cells of the body), which affects approximately 1:2000 female. Principal characteristics are short stature and gonadal disgenesis. Clinical management consist of Growth Hormone (GH) treatment and oestrogen replacement therapy (HRT), to induce development of secondary characteristics and to avoid the sequelae of oestrogen deficiency. Aim of the study: To assess clinical management, quality of life (QoL) and general psychosocial adjustment of women with TS. Population: 70 adult Caucasian females with TS (mean age: 27.8, ± 7.6; range 18-48 y.). Setting: Specialist service for Rare Disease care, University Hospital. Methods: Subjects were required to fill in questionnaires collecting ASR, WHOQOL, and 8 open questions. Data were compared with those of the Italian population or to those collected in a comparison group (70 healthy females, mean age: 27.9, ±7.3, range 21-48 y.). Results: Women with TS are educated as well as the Italian Population, but they have a less successful professional life. They show good QoL in general, but they appeared less satisfied in social area. They had statistically higher scores than the comparison group for depression, anxiety and withdrawal. Are less involved in a love relationship. Diagnosis communication was mostly performed by doctors or parents, satisfaction was higher when information was given by parents. Main preoccupation about TS are infertility, feeling of being different and future health problem. Conclusions: Italian people with TS were generally well adapted and have a good QoL, but lived more often with parents and show impaired sentimental and sexual life. They have higher degree of psychological distress compared to a comparison group. Psychological intervention should firstly address parents in order to encourage an open communication on diagnosis issues and on sexual education.

Role of second trimester ultrasound in prediction of newborns neurologic damage after maternal Cytomegalovirus infection

Objective To find a correlation between cerebral symptoms at birth and abnormalities found at anomaly scan, through the analysis of sensitivity of the anomaly scan in the prediction of severe CMV neonatal disease. Methods - Design, Setting, Population This was a retrospective collection of all cases of primary congenital CMV infection reported in our unit (Obstetrics and Perinatal Medicine, Policlinico di S Orsola, IRCSS, Bologna) over a period of 9 years (2013–2022). Only cases of fetal infection following confirmed maternal primary infection in the first trimester (MPI) and newborns with confirmed CMV infection on blood/saliva or urine were included. Results Between 2014 and 2022, 69 fetuses had an antenatal diagnosis of primary CMV infection. The infection occurred after MPI in the first, second, and third trimester in 63.7% (43/69), 27.5% (19/69), and 10% (7/69) of cases, respectively. Second-trimester assessment by anomaly scan was abnormal in 10/69 (15%) fetuses: 5/69 (7%) had an extracerebral STA and 5/69 (7%) had a cerebral STA. Normal anomaly scan was found in 59/69 (86%) fetuses. When looking at all fetuses infected in the first trimester, 12.5% (5/40) underwent TOP and 45% (18/40) had symptoms at birth. A mean follow-up of 22.4 months (range 12–48 months) was available for 68/69 (99%) live born neonates. Conclusion Anomaly scan results to have a predictive positive value of 67% fetuses infected in the first trimester. Serial assessment by ultrasound is necessary to predict the risk of sequelae occurring in 35% following fetal infection in the first trimester of pregnancy. This combined evaluation by US and trimester of infection should be useful when counselling on the prognosis of cCMV infection.