Clinical and oncological outcomes in single-stage versus staged surgery for pediatric craniopharyngiomas: a multicenter retrospective study.

PURPOSE: Craniopharyngiomas (CPGs) are aggressive brain tumors responsible of severe morbidity in children. The best treatment strategies are under debate. Our study evaluates surgical, pituitary, and hypothalamic outcomes of a tailored staged-surgical approach compared to a single-stage radical approach in children with CPGs. METHODS: Multicenter retrospective study enrolling 96 children treated for CPGs in the period 2010-2022. The surgical management was selected after a multidisciplinary evaluation. Primary endpoint includes the inter-group comparison of preservation/improvement of hypothalamic-pituitary function, the extent of resection, and progression-free survival (PFS). Secondary endpoints include overall survival (OS), morbidity, and quality of life (QoL). RESULTS: Gross Total Resection (GTR) was reached in 46.1% of cases in the single-stage surgery group (82 patients, age at surgery 9 ± 4.7 years) and 33.3% after the last operation in the staged surgery group (14 patients age 7.64 ± 4.57 years at first surgery and 9.36 ± 4.7 years at the last surgery). The PFS was significantly higher in patients addressed to staged- compared to single-stage surgery (93.75% vs 70.7% at 5 years, respectively, p = 0.03). The recurrence rate was slightly higher in the single-stage surgery group. No significant differences emerged in the endocrinological, visual, hypothalamic outcome, OS, and QoL comparing the two groups. CONCLUSIONS: In pediatric CPGs' surgical radicality and timing of intervention should be tailored considering both anatomical extension and hypothalamic-pituitary function. In selected patients, a staged approach offers a safer and more effective disease control, preserving psychophysical development.

Pressing Issues in COVID-19: Probable Cause to Seize SARS-CoV-2 for Its Preferential Involvement of Posterior Circulation Manifesting as Severe Posterior Reversible Encephalopathy Syndrome and Posterior Strokes.

Since December 2019, a novel Severe Acute Respiratory Syndrome coronavirus 2 from China has rapidly spread worldwide. Although respiratory involvement is the mainstay of coronavirus disease 2019 (COVID-19), systemic involvement has recently drawn more attention. In particular, a number of recent articles have shed light on the nervous system as one of the possible targets. At our institution, we observed 15 patients with acute brain vascular manifestations; most interesting, we had a higher prevalence of the posterior circulation acute impairment. In our series, 7 patients had acute posterior cerebral injury: 1, hemorrhagic posterior reversible encephalopathy syndrome; 5, posterior circulation ischemic stroke; and 1, parieto-occipital hemorrhagic stroke. On the basis of our evidence and previous basic science reports, we believe a common etiopathogenetic thread may connect ischemic/hemorrhagic events of the posterior circulation and posterior reversible encephalopathy syndrome in the setting of COVID-19.

How I do it: step-by-step BacJac™ posterior interspinous spacer placement.

BACKGROUND: BacJac™ is a posterior interspinous spacer for selected cases of degenerative lumbar spine diseases. It blocks the metameric vertebral segment in terminal extension, restoring foraminal heights. METHODS: The authors provide a detailed step-by-step description of the surgical technique, shedding light on surgical tips and pitfalls of this procedure. An accurate pre-operative patient selection is analyzed, defining meticulously surgical indications. A high-quality video of the surgical procedure is provided. CONCLUSION: BacJac™ interspinous device allows a safe, mini-invasive, and effective treatment of selected cases of degenerative lumbar spine disease.

Enzyme replacement treatment in type 1 and type 3 Gaucher's disease.

The development of intravenous enzyme-replacement treatment for Gaucher's disease has changed life expectancy in cases without neurological involvement (type 1). The effects in patients with neurological involvement are unknown. We treated 12 Italian patients, types 1 (9) and 3 (3), with intravenous alglucerase: 70-120 IU/kg per month for type 3 and 30-60 IU/kg per month for type 1. Maintenance infusions were biweekly in patients without neurological symptoms, whereas in one symptomatic type 3 patient, infusion was weekly. All patients improved; a resumption of growth in children with growth retardation was observed and spleen and liver reduced in size. In one type 3 patient, a bone callus formed during treatment and enabled the patient to walk. Laboratory tests showed rapid increase of haemoglobin in anaemic patients, and a slower response in patients with thrombocytopaenia. In 4 patients there was temporary hypocalcaemia immediately after the beginning of treatment. Neurological symptoms were present in 1 of the type 3 patients, and electroencephalogram was abnormal in another. After 2 years of treatment, the patient with symptoms showed an improvement of psychomotor skills and of IQ from 50 to 60. Genotype analysis showed a high frequency of the 1448C mutation (54.5%). The 9 patients carrying this allele came from Italian regions which in the past had been invaded from north Europe and Scandinavia. Enzyme replacement in Gaucher's type 1 can also be effective at low doses and even with a 2-week interval between infusions. This makes treatment cheaper, and reduces hospital stay for patients.

Aminohydroxypropylidene-biphosphonate in the treatment of bone lesions in a case of Gaucher's disease type 3.

Gaucher disease is the most prevalent lysosomal storage disorder. It is characterized by an autosomal recessive inheritance of a deficiency of lysosomal acid glucocerebrosidase. Three clinical phenotypes are recognized: type 1 (non-neuronopathic), type 2 (acute neuronopathic), type 3 (subacute neuronopathic). Bone lesions are associated with type 1 and type 3 Gaucher disease. Skeletal involvement is secondary to the progressive accumulation of histiocytes and macrophages laden with glucosylceramide in bone marrow. Our patient was a female type 3 Gaucher patient who was referred to us at the age of 3 years with a neurological symptomatology and severe bone lesions (bilateral fracture of the femur heads, lytic process of the bone matrix of the femurs and distal flask deformity, kyphoskoliosis and chest deformity). The baby was constrained to a wheel-chair. The use of (3-amino-1-hydroxypropylidene)-1,1-biphosphonate (APD) was described in a case of Gaucher disease with very severe bone lesions. We used periodic iv infusions of APD (10 mg every 3 weeks) in our patient for a period of 20 months; after that, enzyme replacement therapy (alglucerase) was commenced. APD treatment showed normalization of bone density, formation of bone callus at the femural heads, positive calcium balance. The urinary Ca/Cr ratio and TRP were consistently normal during therapy. After 9 months of alglucerase therapy the patient was able to walk again. The data indicate that APD therapy can find an indication in Gaucher patients with severe bone involvement.

1448C mutation linked to the Pv1.1- genotype in Italian patients with Gaucher disease.

Gaucher disease is the most common of the glycolipid storage diseases and is caused by an inherited deficiency of the enzyme glucocerebrosidase. It is a very heterogeneous disease and presents early and late onset forms which may or may not be associated with a neurological disease. Several point mutations of the glucocerebrosidase gene have been reported to cause this disease. This is the first report of the mutations causing GD in Italy. In this study of ten patients of non-Jewish origin, two mutations (1226G and 1448C) accounted for 19 of 20 disease alleles. In these patients a gene frequency of 33% for the 1226G mutation and 57.8% for the 1448C mutation was found. The patients homozygous for the 1448C mutation were also homozygous for the Pv1.1- genotype (polymorphic Pvu II site present at nt. 3931). This is in contrast with previous reports linking 1448C mutation to the Pv1.1+ genotype. Two out of the three 1448C homozygous patients are currently free of any evident neurological symptoms. These patients have been undergoing enzyme-replacement therapy for the last one year and have a Pv1.1-/1448C glucocerebrosidase haplotype. Both these factors appear to be associated with a late development of neuronopathic disease.

Low incidence of GvHD and rejection after pharmacological ex vivo modulation of bone marrow in 2-3 antigens mismatched BMT.

2-3 antigens mismatched BMT were performed on 32 children without a matched sibling donor. In the light of previous in vitro studies, which suggested a role of Vincristine and Methilprednisolone ex vivo treatment in modulating alloreactivity of T cells, bone marrow was treated with such a pharmacological cocktail before being infused. Acute GVHD 2 degrees to 4 degrees degree occurred in 46% of cases, chronic GVHD in 28%, graft failure in 13%. There was no significant difference between 2- and 3-antigens mismatched BMT as far as GVHD and graft failure are concerned.

Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells.

Five young patients with Niemann-Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30-40% of the assays.

[Comparison of high-dose immunoglobulin and cyclosporine in newly diagnosed diabetic children]. / Confronto fra immunoglobuline ad alte dosi e ciclosporina in bambini diabetici all'esordio.

A controlled trial was carried out on type I diabetic children to evaluate and to compare the clinical effects of two different kinds of immunotherapy: high doses intravenous gammaglobulin (IVIgG) and cyclosporine A (CyA). 30 newly diagnosed patients were admitted to the trial, 10 of whom served as controls (group A), 10 received 400 mg/kg b.w. of IVIgG on 5 consecutive alternate days and subsequently after 15 days and monthly thereafter for up to six months (group B), 10 patients received CyA 5-10/kg b.w. by mouth in two daily doses for a period comprised between 6 and 18 months (group C). Serum post-prandial C-peptide level was significantly higher after 6 months in group B and C than in group A; after 12 months, only group C showed significantly higher values. This difference was no longer significative at 18 and 24 months. Insulin requirement in the treated groups was significantly lower than in control group at 6 months, this difference was no longer significative at 12 months. We didn't find any difference concerning insulin requirement during the study comparing the two groups treated with the two different immunosuppressive therapies. In 3 patients in group B and in 3 patients in group C we didn't observe any appreciable response to immunosuppressive therapy (defined as insulin requirement greater than 0.5 UI/kg b.w. at 6 months and/or greater than 0.8 UI/kg b.w. at 12 months). We couldn't find any significant difference between responders and not responders to the immunosuppressive therapies regarding age, symptoms lasting before the diagnosis, weight loss, ketoacidosis intensity and serum post-prandial C-peptide level at the onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal permeability, atopic eczema and oral disodium cromoglycate.

A dual sugar (lactulose-mannitol) absorption test was performed in 19 patients with atopic eczema before and after a 21 day elimination-diet. Moreover L/M test was carried out in 20 controls. The mean value of lactulose-mannitol urinary ratio (L/M) was 0.015 (+/- 0.018 SD) in the group of patients and 0.012 (+/- 0.011 SD) in the control group (p = 0.49). The mean clinical score improved significantly after elimination diet (41,6 +/- 12.9 SD before the diet, 21.7 +/- 10.4 SD after the diet, p less than 0.001) but no significant modification of intestinal permeability was recorded (L/M = 0.015 +/- 0.018 SD before the diet and 0.21 +/- 0.022 SD after the diet, p = 0.38). Using a double blind approach we were not able to demonstrate any significant effect of disodium cromoglycate on the clinical score and intestinal permeability. The connections between food allergy, intestinal permeability and atopic dermatitis have not been understood, but disodium cromoglycate doesn't seem to play a significant role in the treatment of atopic dermatitis nor in the modification of intestinal permeability.

[Bone marrow transplantation in pediatrics: its current status, the problems and prospects]. / Il trapianto di midollo osseo in pediatria: stato attuale, problemi e prospettive.

Notwithstanding the high proportion that achieve a cure after chemotherapy, there are still a case in which only a BMT can offer a chance of cure. This minority of patients can undergo an allogeneic BMT if a HLA matched donor is available or an autologous BMT if a good remission is achieved before the BMT. Not all the patients comply with these criteria. Therefore we need to widen the availability of the donors searching for unrelated matched donors or facing the problems of an aplohidendical BMT. The efforts to treat even children with advanced disease are based on the possibility of overcoming the blasts resistance or of stimulating the non-HLA restricted cytotoxicity with IL2.

[Evaluation of the effectiveness of thymomodulin in children with recurrent respiratory infections]. / Valutazione dell'efficacia della timomodulina in bambini con infezioni respiratorie ricorrenti.

Numerous trials of prophylaxis of recurrent respiratory infections in children have been performed, even though the only controlled trials providing incontrovertible results were the ones carried out with levamisole and thymostimulin through intramuscular administration. We have experimented a calf-thymic extract administered by oral route (thymomodulin). During the summer we enrolled 40 children aged between 3.5, and 9 years who had suffered from RRI during the previous winter. The patients were randomly divided in two groups and respectively treated with thymomodulin or with placebo; 21 children were given the thymic extract and 19 the placebo. The trial was carried out according to a double-blind schedule for a period of four months, from the beginning of October '84. At the end of the trial we assessed the catharral bouts observed during the research period by the family doctors and the parents evaluation on the clinical state. The difference between the two groups is statistically highly significant both with reference to the reduction of the total number of catharral bouts and to the general clinical state according to the parents opinion. The research clearly demonstrates the protective effect of the thymomodulin, probably due to the "restorative" effect on some immunological functions, temporarily compromised during the infection bouts.

Immunological patterns in monoarticular juvenile rheumatoid arthritis.

Seven pediatric patients with monoarticular arthritis, three of whom had a recent onset form and the remaining four a disease of longer duration, were examined for possible modifications of their immunological parameters. The diagnosis of JRA was made on all these patients according to the ARA criteria after a follow-up of at least two years. Humoral and cellular abnormalities of the immune system were searched for in peripheral blood, synovial fluid and synovial membrane. No evidence for complement consumption and for increased levels of immune-complexes was found in the sera and in the synovial fluids of these patients, who were all seronegative. Some patients had antinuclear antibodies in their sera and synovial fluids. With regard to the lymphocyte distribution, whereas only some patients had an increased number of circulating B cells, the majority had a decreased CD4+/CD8+ ratio in the synovial fluid compared to the ratio found in the peripheral blood. A massive infiltration of CD4+ cells and macrophages and the presence of a substantial number of OKT9+ cells was found in the synovial membranes.

[Long-term remission induced by measles infection and followed by immunosuppressive therapy in a case of refractory juvenile rheumatoid arthritis]. / Remissione a lungo termine in caso di artrite reumatoide giovanile intrattabile indotta da infezione morbillosa seguita da terapia immunosoppressiva.

A case of severe juvenile rheumatoid arthritis, polyarticular type, refractory to FANS and long acting therapy which showed a quick remission after measles is described. An immunosuppressive therapy to strengthen the immunosuppression induced by virus infection was performed for six months. The remission has been maintained for 4 years and appears up to now to be stable with no therapy. On the basis of this observation, the possibility of a vaccination therapy with measles virus, which equally gives immunosuppression, is discussed.

Successful therapy of Niemann-Pick disease by implantation of human amniotic membrane.

In a patient with a lysosomal storage disorder, not involving the CNS, repeated implantations of human amniotic sheets have proved to provide a successful approach to enzyme replacement therapy. Implantation of pure epithelial cells, separated from the other cell types of the amnion, might markedly improve the procedure, avoiding some risks of host-versus-graft rejection.

[Therapy with plasmapheresis and lymphoplasmapheresis combined with immunosuppressive agents in 2 cases of intractable juvenile rheumatoid arthritis]. / Terapia con plasmaferesi e linfoplasmaferesi associata ad immunosoppressore in due casi di artrite reumatoide infantile intrattabile.

Two cases of JRA refractory to NSAID' steroids and long-acting drugs were successfully treated with plasmapheresis and combined lympho- and plasma-apheresis respectively. Case 1. A 8 year old female child who had been suffering from systemic JRA for 6 years received a course of three plasmapheresis followed by a 6 month cycle of azathioprine. Clinical and laboratory remission was promptly achieved and is still present after 18 months. Case 2. A 12-year old boy affected by poliarticular JRA received a course of 4 plasmapheresis followed by a 6 month cycle with azathioprine. The opportunity of performing plasma or lymphoplasmapheresis reinforced by immunosuppressive drugs such as azathioprine or methotrexate at low doses in refractory cases of JRA is discussed.

[Graft of cryopreserved human amniotic epithelial cells in a subject with type B Niemann-Pick disease]. / Impianto di cellule epiteliali amniotiche umane crioconservate in un soggetto affetto da malattia di Niemann-Pick tipo B.

Implantation of pure cryopreserved epithelial cells obtained by enzymatic digestion of human amnion was successfully carried out in one patient affected by Niemann-Pick disease type B. No host-versus-graft reaction was recorded after implantation. The clinical improvement observed in this patient is supposed to be effect of the documented increase of sphingomyelinase activity in his leukocytes after implantation, confirming the possibility that an effective release of sphingomyelinase from amniotic epithelial cells and enzyme uptake by deficient cells can occur. Separation and cryopreservation of human amnion epithelial cells markedly improve the procedures of implantation and may represent a further step beyond in the enzymatic therapy of many lysosomal storage disorders.