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To assess the correlation between menopausal symptoms and pain caused by temporomandibular disorder (TMD) and the impact of sociodemographic factors on the association.In this cross-sectional study, a total of 74 women with TMD symptoms were enrolled and divided into three groups according to the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria: G1 (n = 25, late menopausal transition), G2 (n = 30, early postmenopause), and G3 (n = 19, late postmenopause). Sociodemographic data were collected, along with data on menopausal symptoms (Blatt-Kupperman menopausal index) and TMD-induced pain (craniomandibular index). Statistical analysis was performed using a chi-squared test and linear correlation tests (Spearman and Pearson).Analysis of the three groups showed that TMD-induced pain was more intense in G1 than in G3 (P = 0.0426, r = 0.2364, r2 = 0.05589), and menopausal symptoms correlated with the intensity of TMD-induced pain (P = 0.0004, r = 0.4020). This correlation was more significant during the late menopausal transition (G1: P = 0.0267, r = 0.4427, r2 = 0.1960). In G2, women with fewer than 4 years of schooling had a higher total Blatt- Kupperman menopausal index score (17.0 ± 85.0) and craniomandibular index (0.29 ± 0.23) than women with more than 4 years of schooling (P = 0.02 for both indices).Our results suggest that TMD-induced pain and menopausal symptoms are correlated, and more strongly so in the late menopausal transition. Additionally, sociodemographic factors, such as schooling, have a major influence on symptoms in early postmenopause. Performing the TMD evaluation during the climacteric period may be important.

Purpose: The volume of data produced by the biomedical research community continues to grow rapidly. Efficient collection, curation, and sharing of these data are expected to enable researchers to synthesize larger datasets and apply novel methods to discover new patterns for diagnosis, treatment, and care of disease. Consequently, data platforms that support these functionalities have become an important instrument for the biomedical research community. The National Cancer Institute’s (NCI’s) Cancer Research Data Commons (CRDC) is a data platform for the cancer research community that provides cloud-based, secure storage and analytic tools for cancer data, including genomics, proteomics, imaging, and clinical trial data. CRDC has been funded by multiple sources, including the Beau Biden Cancer Moonshot program. Achieving long-term sustainability of the CRDC program is the focus of our study. Methods: We applied a Financial Operations (FinOps) framework to map all costs to functionalities provided by the CRDC, including processes such as data intake, storage, compute, user support, and project management. We established a comprehensive financial baseline for the operations of the CRDC, identified opportunities for optimization across multiple dimensions (people, processes, technology), projected future costs based on trends for cancer data, and evaluated sustainability under defined funding scenarios. Results: We identified 15 recommendations for optimization of the CRDC, including automation and centralization of core services (e.g., intake, curation, indexing), optimization of storage (e.g., compression, archiving), and harmonization of common services across the CRDC components (e.g., common architecture, governance). If implemented, we could demonstrate that these recommendations offer a path to long-term sustainability of the CRDC program under a variety of funding scenarios. Conclusion: Data platforms such as the CRDC will see rapid increases in operational costs due to the growing data volumes and demand from researchers. Optimizing governance and operational frameworks will result in efficiency gains that can ensure long-term sustainability. Taking these steps will be critical to provide the necessary infrastructure to advance the field of data-driven biomedical research. Citation Format: Juergen A. Klenk, Angela Maggio, Bhavani S. Singh, Erin N. Byrne, Erika Kim, Tanja M. Davidsen. A path to sustainability for the National Cancer Institute's Cancer Research Data Commons. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6582.

BackgroundInherited thrombocytopenias (ITs) are rare congenital bleeding disorders characterized by different clinical expression and variable prognosis. ITs are poorly known by clinicians and often misdiagnosed with most common forms of thrombocytopenia.Material and methods“CHildren with Inherited Platelet disorders Surveillance” study (CHIPS) is a retrospective – prospective observational cohort study conducted between January 2003 and January 2022 in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). The primary objective of this study was to collect clinical and laboratory data on Italian pediatric patients with inherited thrombocytopenias. Secondary objectives were to calculate prevalence of ITs in Italian pediatric population and to assess frequency and genotype–phenotype correlation of different types of mutations in our study cohort.ResultsA total of 139 children, with ITs (82 male - 57 female) were enrolled. ITs prevalence in Italy ranged from 0.7 per 100,000 children during 2010 to 2 per 100,000 children during 2022. The median time between the onset of thrombocytopenia and the diagnosis of ITs was 1 years (range 0 - 18 years). A family history of thrombocytopenia has been reported in 90 patients (65%). Among 139 children with ITs, in 73 (53%) children almost one defective gene has been identified. In 61 patients a pathogenic mutation has been identified. Among them, 2 patients also carry a variant of uncertain significance (VUS), and 4 others harbour 2 VUS variants. VUS variants were identified in further 8 patients (6%), 4 of which carry more than one variant VUS. Three patients (2%) had a likely pathogenic variant while in 1 patient (1%) a variant was identified that was initially given an uncertain significance but was later classified as benign. In addition, in 17 patients the genetic diagnosis is not available, but their family history and clinical/laboratory features strongly suggest the presence of a specific genetic cause. In 49 children (35%) no genetic defect were identified. In ninetyseven patients (70%), thrombocytopenia was not associated with other clinically apparent disorders. However, 42 children (30%) had one or more additional clinical alterations.ConclusionOur study provides a descriptive collection of ITs in the pediatric Italian population.

Background: Subclinical hyperthyroidism is defined by a subnormal serum thyroidstimulating hormone (TSH) level with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels. Its prevalence varies from 0.6% to 16% in the elderly and can increase to 20% in patients receiving thyroid hormone replacement therapy. Thyroid disease and/or replacement therapy are frequently associated with cardiovascular involvement. Cases Presentation: We report three clinical cases of patients with initial subclinical hyperthyroidism and cardiological manifestations, including supraventricular and ventricular extrasystoles, prolapse of the mitral valve with severe regurgitation, higher mean heart rate and deterioration of the arrhythmias on arrhythmogenic dysplasia substrate. Conclusion: We discuss the role of appropriate and early correction of thyroid dysfunction in improving cardiological manifestations.

Friedreich's ataxia is a rare degenerative neuromuscular disorder, caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene, with a broad clinical phenotype characterized by progressive gait and limb ataxia, dysarthria, and loss of lower limb reflexes; cardiac involvement is represented by hypertrophic cardiomyopathy, ventricular arrhythmias, and sudden cardiac deaths. Currently, no definite therapy is available, while many drugs are under investigation; for this reasons, we need markers of short‐ and long‐term treatment efficacy acting on different tissue for trial evaluation. We describe the case of a 21‐year‐old patient affected by Friedreich's ataxia on wheel‐chair, with initial cardiac involvement and electrocardiographic features characterized by thiamine treatment‐related negative T wave and QTc variations. We discuss plausible physiopathology and potential ECG role implications as an intermediate marker of treatment response in future clinical trials considering patients affected by Friedreich's ataxia.

Background. Pheochromocytoma is a rare neuroendocrine tumor, clinically characterized by high blood pressure, palpitations, and headache. It is often associated with abnormalities of the ventricular repolarization phase; the dispersion of ventricular repolarization is the basis for ventricular arrhythmias (torsion de point, ventricular tachycardia or ventricular fibrillation). Objectives. Analysis of abnormal ventricular repolarization focused on the presence and amount of U wave in patients affected by pheochromocytoma and its modification after surgery. Materials and Methods. We reviewed pathology records of 722 patients admitted for adrenal nodule or suspected chromaffin-cell tumor and identified 39 patients affected by pheochromocytoma. Metanephrine, normetanephrine, and 3-methoxytyramine have been assessed by determining concentrations in 24-hour urine collection. Standard 12-lead electrocardiogram records have been reviewed with analysis of heart rate, P wave, PR interval, QRS duration, QTc, and U wave. Then we selected and compared 22 patients of 39 affected by pheochromocytoma, with both clinical and electrocardiographic data before and after surgery. Results. In our cohort of 39 patients affected by pheochromocytoma, we found U wave in ECG, before treatment, in 82.8 percent of patients, while only 37.0 percent after treatment (p2=0.333, p=0.015), 3-methoxytyramine levels (r2=0.458, p=0.006), and tumor size (r2=0.429, p=0.003). Conclusions. In our retrospective analysis, patients affected by pheochromocytoma presented U wave in electrocardiogram. The presence and amount of U wave were associated with the metanephrine levels and the tumor size with significant reduction after surgical removal.

The association between celiac disease (CD) and immune thrombocytopenia (ITP) is still uncertain. The aim of this study was to characterize the coexistence of these two diseases in Italian children.This is a retrospective multicenter study investigating the occurrence of CD in 28 children with ITP diagnosed from January 1, 2000, to December 31, 2019.The first diagnosis was ITP in 57.1% and CD in 32.1% of patients. In 3 patients (10.7%), the two diagnoses were simultaneous. All the potential and silent cases of CD in our cohort were diagnosed in the groups of “ITP first” and “simultaneous diagnosis”. In all children ITP was mild, and in 2 out of 8 not recovered from ITP at the time of CD diagnosis a normalization of platelet counts (100,000/μL) occurred 3 and 5 months after starting a gluten-free diet, respectively.We think that screening for CD should be considered in children with ITP regardless of the presence of gastrointestinal symptoms. Furthermore, some patients may recover from ITP after starting a gluten-free diet.İmmün trombositopeni (İTP) ve çölyak hastalığı (ÇH) arasındaki ilişki hala belirsizliğini korumaktadır. Bu çalışmanın amacı İtalyan çocuklarında bu iki hastalık arasındaki ilişkiyi ortaya koymaktır.Bu çalışma, 1 Ocak 2000’den 31 Aralık 2019’a kadar İTP tanısına ek olarak ÇH tanısı alan 28 çocuğun araştırıldığı geriye dönük çok merkezli bir çalışmadır.Hastaların %57,1’inde ilk tanı İTP ve %32,1’inde ÇH idi. Üç hastada (%10,7) iki tanı aynı anda konulmuştu. Kohortumuzdaki tüm potansiyel ve sessiz ÇH olguları “önce İTP” ve “eşzamanlı tanı” gruplarında teşhis edildi. Tüm çocuklarda İTP hafifti ve ÇH tanısı sırasında trombositopenisi devam eden 8 çocuktan 2’sinde, glutensiz diyete başladıktan sonra sırasıyla 3 ve 5 ayda trombosit sayılarında normalleşme (100.000/μL) görüldü.Bu çalışma İTP’li çocuklarda gastrointestinal semptomların varlığına bakılmaksızın ÇH taramasının yapılması gerektiğini düşündürmektedir. Bazı hastalarda trombosit sayılarının glutensiz bir diyete başladıktan sonra düzelebileceği akılda bulundurulmalıdır.

Objectives This study aimed to evaluate the effects of acupuncture on women with vasomotor symptoms during the menopausal transition with the aid of the Kupperman-Blatt Menopausal Index. Method Crossover, single-blind, sham-controlled trial with 100 women randomly divided into two groups of 50 participants each: G1 and G2. During the first 24 weeks of treatment, the G1 women received acupuncture and the G2 women were given sham acupuncture. The crossover was then applied: the G1 participants were given sham acupuncture, and the G2 participants received acupuncture for 24 more weeks. Results The mean score of hot flashes of the group who first experienced acupuncture (G1) was statistically higher than that of the group that started with sham acupuncture (G2, P = 0.020). Also, both groups had similar mean scores in the middle of the study (both were receiving acupuncture). During the last 6 months of the study, after crossover, the values of G2 (acupuncture) were lower than those of G1 (sham acupuncture). Conclusions Acupuncture treatment may mitigate hot flashes and other climacteric symptoms during the menopausal transition. : Video Summary:http://links.lww.com/MENO/A641.

Purpose The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a cross-sectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results The age of the patients on their first clinic visit ranged from 65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes (n = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the body mass index (BMI) found decreases in BMI with increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n = 70) were between 65 and 69 years of age, 8.97% (n = 7) were between 70 and 74 years of age, and only 1.28% (n = 1) of those were aged older than 75 years. Conclusions Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women.

Objectives: Despite the correct application of blood transfusions and chelation treatments, beta thalassemia patients have many complications. Systematic population analyses on types and frequency of these complications are very few. The aim of this study is to characterize the complications, their risk factors and their clinical and economic impact. Methods: Complications at baseline and events occurring during one observational year were analyzed in 272 patients aged >12 years. Risk factors were analyzed through chi-squared and unpaired t tests. Logistic regression was applied to perform the risk factors multivariate analysis. Results: A total of 554 complications (1–6 per patient) affected 82.3% of patients. Cardiac complications were less represented than expected. Musculoskeletal diseases were the most represented complications followed by hepatic, sexual and endocrine diseases. Splenectomized patients, born before 1970 and aged >40 years, starting iron chelation therapy when aged >4 years or after receiving more than 20 blood transfusions, presented a significantly higher number of complications. A total of 885 adverse events requiring 34125 additional medical services occurred in 1 year. Of these, 34.9% were related to treatments and 65.1% to other causes. Event numbers, additional medical interventions and cost increased progressively in patients affected by one or more complication compared to patients with no complications. Conclusions: The pattern of complications changes according to birth cohort and differentiates older from younger patients. The burden of the disease and its costs increase after the onset of the first complication, therefore prevention of complications is fundamental in these patients.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating illness, characterize-ed by a monophasic course frequently associated with infections or previous immunization. Regarding pathogenesis, encephalomyelitis is associated with some immunological mechanisms. Post-infection or post-vaccination inflammatory reactions in the perivenular region in the central nervous system (CNS) may be explained by a molecular mimicry mechanism. An antecedent infection was identified in 72–77% of paediatric patients. We present a case of a 5 year-old girl in follow up for autoimmune thrombocytopenia (AT) and autoimmune haemolytic anaemia (AHA) in steroid treatment, with history of left hemiparesis, language delay, from as a consequence of perinatal suffering, who has developed ADEM. This patient presented with progressive weakness of limbs, neck pain associated with fever from one day. It was acute in onset and gradually progressive. She became quickly hypotonic and hyporesponsive and had reduced level of consciousness. Within 12 hours of admission, the patient developed sphincter incontinence and dysphagia. After exclusion of papilloedema, lumbar puncture has been performed. An urgent MRI was performed, which showed multiple subcortical lesions of varying size showing hyperintensities in TR at the bridge and in T2 at the medulla . Cerebrospinal fluid (CSF) study showed cell count of 40 cells/mm3 , protein 58 mg/dL, glucose 54 mg/dL. No oligoclonal bands were present in CSF. Blood and CSF cultures were negative like other infectiological analyzes. Also CSF-PCR for the presence of bacteria and virus was negative. Her autoimmune profile with antinuclear antibody was also negative. The clinical features and the MRI findings were suggestive of ADEM. Partial quadriplegia, and reduction of reflexes, as seen in the myelitic form of ADEM, were present. She had developed ADEM while on the maintenance dose of prednisolone. After diagnosis, intravenous methylprednisolone was given at 30 mg/kg daily for 5 days. After 48 hours there was a significant improvement in the patient‘s clinical condition. A regimen of oral steroid was advised after intravenous therapy . The patient responded well to steroid therapy. No residual lesion was found on follow-up. AT and AHA are relatively uncommone. There are studies postulating the possibility of a combination of several autoimmune diseases. Very few cases have been found with this rare association in the literature. Follow-up of these patients is essential for detecting the development of other autoimmune disease in such cases.

Porphyrias are a group of inherited metabolic disorders of heme biosynthesis leading to excessive accumulation and excretion of porphyrins.The variable clinical manifestations may determine a delay in the diagnosis, followed by a possible negative clinical outcome. We describe a case of a 14-year-old girl with Shwachman-Diamond syndrome (SDS) and epilepsy admitted with severe cyclic abdominal pain not responsive to antalgic therapy, localized in the epigastric area, irradiating to the whole abdomen and the back, associated to aspecific symptoms (diarrhea, fever,vomiting). During hospitalization, the girl was asymptomatic. We excluded infectious, autoimmune, endocrinological causes, a relapse of SDS and performed a screening for porphyria that resulted negative. After each attack, she referred presenting urinary retention followed by hyperchromic urines, anxiety and paresthesias. Past clinical data showed hyponatremia, tachycardia and hypertension. Eventually, increased values of ALA (8.21 mg/l) and PBG (3.96 mg/l) were found; exposure of fresh urines to sunlight caused a change of their color. Finally, genetic analysis was negative. These findings allowed the diagnosis of porphyria, therefore we prescribed a normocalorichyperglucidic diet andpreventive glucose solutions in stressing situations, with regression of symptoms. Acute porphyrias present with life-threatening crisis secondary to the injury of central, peripheral and autonomic nervous system. They can be triggered by drugs, alcohol, infections, reduced caloric intake, endogenous hormone cycles and stressing situations. The characteristic manifestations are severe cyclic abdominal pain, neurological or psychiatric symptoms and/or hyponatremia. Diagnostic is the assessment of plasmatic PBG/ALA, always increased during an attack, normal during remission. Treatment is human haemin although, in mild attacks, a diet with high carbohydrates and/or preventive glucose infusions is effective; a negative genetic evaluation should never exclude the diagnosis. It is important considering acute porphyria in the differential diagnosis of severe cyclic abdominal pain, particularly in subjects affected by different and/or rare clinical disorders.

Autoimmune hemolytic anemia (AIHA) is an uncommon disease of childhood caused by the premature destruction of erythrocytes by autoantibodies. In this rare disease both diagnostic criteria and therapeutic approaches are not well standardized. The Red Cell Working Group of the Pediatric Italian Hematogy and Oncology Association (AIEOP) developed specific recommendations to help Physicians for AIHA management. The document is available on the AIEOP website since November 1st 2013. The Italian Pediatric AIHA Group began an observational, retrospective and prospective study in order to monitor the management of children with AIHA diagnosed from 2010 to 2018, and to assess whether the availability of AIEOP recommendations had an impact on the clinical management of such patients in AIEOP Centers. We collected a national cohort of 159 children with AIHA from 21 AIEOP Centers; 48 patients were diagnosed before November 2013 and 111 patients after that date. Gender was 56% males and 44% females; median age at diagnosis was 47 months, with 11.9% under 12 months of age; 8.2% of children were born prematurely and 3.9% showed congenital malformations. 23.2 % of patients had a familiar history of immunological, hematological or oncological diseases. The median hemoglobin level at diagnosis was 6.1 gr/dL. Table 1 reports the distribution of our cases, according to the different type of autoantibodies. The comparison between the retrospective and prospective study did not reveal significative differences in clinical and biological presentation. The cold IgM forms were mainly post infective (38.4%) or primary forms (53.8%), only one patient had a secondary form due to a primitive immunodeficiency. These patients did not develop other diseases during follow up (median follow up: 28,6 months). The preliminary results of treatment and follow up of the 146 patients with warm antibody AIHA revealed the following: The treatment with conventional dose of steroids (median dose 2 mg/Kg, range 0.7- 3.5 mg/Kg) was started in 94.4% of patients, in 53% of cases on the same day of diagnosis. A high number of children used additional treatment: red blood cell transfusions (51.4%), high dose Prednisolone (59.7%), high dose i.v. Immunoglobulin (49.7%) and Plasma Exchange (1.4%). 9.5% of patients, with poor responsive disease, needed alternative drugs during the first four weeks of therapy. Response criteria were so defined: a complete response was defined as the achievement of an Hb concentration greater than or equal to the lower normal limit for age with no signs of haemolysis, i.e. normal reticulocyte count and bilirubine concentration. A partial response was defined as an increase of Hb >2 g/dL without the Hb concentration reaching a normal value for the patient age and no response as an increase of Hb< 2 g/dL and/or dependence on transfusion. A complete response was reached by 62.5%, 79.3%, 85.1% at 3, 4, 6 weeks respectively. 14.9% of patients had either a partial response or a resistant disease at 6 weeks. IgG/IgG+C3d positivity was a negative prognostic factor, as compared to positivity to C3d only, with the need of a second line treatment (prevalently Mabthera or Mycophenolate Mofetil) in 31.7% vs 0, respectively (p 0.009). Currently 6.1% of the patients were lost to follow up, 1.3% died, 55,8% are in Complete Response without events and 21.9% of the patients are still on treatment . At the last follow up, in the whole "cohort" of warm AIHA, 58% have a Primary form, 15.7% an isolated post infective form and 27.7% a Secondary form (56% Evans Syndrome). The management of the patients diagnosed after November 2013 was mostly in agreement with our recommendations, whose comprehensive therapeutic algorithm is reported in table 2, with prolonged steroid tapering in order to extend the treatment for at least 6 months. The most important difference between the retrospective and prospective study was the duration of first line treatment: 6 months or more, for steroid dependence, in 71.6% of patients in the prospective study versus 52.3% of the retrospective (p 0.031) and, more importantly, the percentage of relapsed patients: 8.3% in the prospective study versus 29.8% of the retrospective (p 0.001), these data need a longer follow up (median follow up: 24 months in the prospective study versus 63 in the retrospective) Disclosures Colombatti: Global Blood Therapeutics: Consultancy; Novartis: Consultancy; AddMedica: Consultancy.

Brain tumours are the most frequent solid tumours and the first cause of cancer-related death in childhood. Their diagnosis has been increasing due to the improvement of diagnostic tools. Low-grade gliomas and embryonal tumours are the most frequent (50% and 20%, respectively). A 10-month-old male presented with hyporeactivity, drowsiness, right arm hypomobility and inappetence. Hospitalised, his Fundus Oculi which showed papilla with regular margins, lightly congested and raised. EEG revealed slow track and specific activity in the back left temporal region. Gadolinium-MRI of the brain revealed a cystic tumour of 7 × 9×12 cm, with intense and heterogeneous enhancement that involved the left cerebral hemisphere. The mass compressed the left and third ventricle and the brainstem was shifted beyond the median line. The right ventricle was expanded and there was sweating of cerebrospinal fluid for the Monro’s foramen obstruction. The patient underwent complete exeresis of tumour. Histology confirmed diagnosis of Desmoplastic Infantile Astrocytoma/Ganglioglioma (DIA/DIG), grade I WHO. Immunophenotype: astrocytic (GFAP, Vimentin), neuronal (synaptophysin). MIB-1: 5%. After hospitalisation, the patient started rehabilitation with a gradual recovery of motor functions. Actually at 30 months of follow up the patient is free of disease and healthy. DIA/DIG is a rare paediatric brain tumour (1.25% of brain tumours), characterised by divergent glioneuronal differentiation and intense desmoplasia. Superficial in location and affecting mainly the frontotemporal region, it presents as a large, cystic, often dura-attached mass in patients younger than 2 years of age. On MRI, they are large hypodense cystic masses with a solid isodense or slightly hyperdense superficial portion. The histologic diagnosis is characterised by the presence of astrocytic, neuronal, and primitive neuroectodermal markers. The treatment of choice is radical surgical excision, which does not require additional treatment. Post-operative clinical and MRI controls should be used when only partial tumour removal can be performed; indeed, long-term stability or complete disappearance of the tumour residual may follow even an incomplete surgical tumour removal. Chemotherapy is used in partial exeresis and progressive disease; radiotherapy is a last resource. DIA/DIG diagnosis is crucial as they share some neuroradiological and histological findings of malignant brain tumours.

Background Pulmonary embolism (PE) is a potentially lethal condition. Although it’s usually manifested with severe symptoms causing right ventricular dysfunction or haemodynamic instability, in case of partial arterial obstruction it can be asymptomatic. Cancer patients are at high risk of thromboembolic complications. The use of contrast-enhanced computerised tomography for cancer staging has documented a high incidence of asymptomatic PE. Case presentation We present a case of unsuspected PE in paediatric oncology patient. A 10-year-old boy presented with cervical and axillary lymph node swellings. No response to antibiotic therapy. Infectivological tests (mononucleosis, tuberculosis, toxoplasmosis…) were negative. Staging imaging revealed a positron emission tomography/computed tomography (PET-CT) avid anterior mediastinal lymph node. There weren’t liver, spleen and lung injury. Excisional biopsy of the lymph node was consistent with an anaplastic large cell lymphoma ALK+, t(2;5). After positioning of central venous catheter (CVC), the patient began treatment with chemotherapy with reduction of the lymphadenopathy. Subsequently, repositioning of CVC due to malfunction and displacement. After three months, he performed restaging; CT showed bilateral thromboembolism of the pulmonary arteries with partial obstruction. Echocardiogram showed a blood pressure’s increase in pulmonary artery (PAP 38 mmHg) but the child didn’t present respiratory and cardiac symptoms. Echo-color-doppler didn’t report venous thrombosis of the legs. Laboratory tests showed high platelet count. d-dimer levels and activated partial thromboplastin time value were increased. Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) were normal. The patient discontinued chemotherapy and started standard anticoagulant treatment. Two weeks later, CT and ultrasound controls displayed substantial reduction of the obstruction of the pulmonary arteries and decrease of PAP. Conclusions Thromboembolic complications are frequent in children with lymphoma. Often, routine thoracic MDCT examinations of paediatric oncology patients reveal cases of unsuspected PE. It is necessary to identify children at an increased risk for the development of PE to define an appropriate management. However, recent studies have showed that the lack of diagnosis and treatment do not have a negative influence on patient outcome.

Meningioangiomatosis(MA) is a rare malformative or hamartomatous lesion involved in meninges and cortex. Although it was originally described in association with NF-2, recent studies have revealed that it occurs more frequently in sporadic form. The pathogenesis remains unclear. MA has distinct histological and biological features to meningioma(M) but their association(MA-M) isn’t unfrequent. Case report a 12-years-old male was referred to our paediatric division for a history of headhache associated to malformative lesions shown at a first radiological investigation (CT and MRI) done in other hospital when he was 6 years old. At that time, neurosurgeons recommended follow up program. The lesions haven’t change over the years, as shown at the follow-ups, however the persistence of headhache induced the family to request a second opinion. Our physical examination showed mental retardation. He had no family history or stigmata of NF2 and no seizure’s history, electroencephalography didn’t show anomalies. A head CT scan showed the presence of a right hyperdense single mass with gyriform signal pattern and clumped intralesional calcifications. MRI showed an intracranial mass measuring 2x3 × 2.5 cm located in the right posterior frontal cortex. The lesion was hyperintense on T2-weighted imaging and weakly hypointense on T1W1, with ring-like enhancement. MRI confirmed gyriform signal pattern associated to focal areas of cortical fronto-parietal dysplasia. The diagnosis of MA was made. Our patient didn’t present seizure and the lesions appeared stable compared with the previous MRI so, in compliance with the neurosurgeon’s advice, we established a long-term follow up program in association with symptomatic therapy for headhache. MA occurs mainly in children and younger adults with male predisposition, suffering from intractable seizure and less frequently headhache. Atypical symptoms included vomiting, diabetes insipidus, facial weakness, muscle atrophy and pain. MA is a single lesion usually stable or slowly growing. Imaging diagnoses for MA is difficult. The most common finding on CT is a round, single, hypodense mass with varying degrees of calcification. On MRI, the lesions seem confined to the cortex. On T1WI, MA shows a low or iso-intense signal, on T2WI lesions are more frequently hyperintense, but sometimes they can be hypointense. A gyriform signal pattern is common on either CT or MRI, typical of sporadic MA and it’s helpful to distinguish pure MA from MA-M.

Case report L.F., 11 year old boy with neurofibromatosis type 1 (NF1), was admitted to our Clinic for headache. During hospitalisation were performed: 24 hour blood pressure monitor documenting isolated systolic hypertension grade I, Doppler ultrasound of renal vessels which diagnosis of the left renal artery severe stenosis (confirmed at angiography) and MRI brain highlighting extra-axial lesion (1.2 cm) in posterior cranial fossa (PCF). Nifedipine (10 mg/day) therapy was started, and subsequently intravascular stent was placed in renal artery. Neuroradiological control (MRI) showed increased in brain lesion (>2 cm). Surgical removal and histological evaluation allowed diagnosis of hemangioblastoma, with diagnostic suspicion for Von Hipple Lindau syndrome (VHL), confirmed by genetic analysis. Conclusions NF1 is an autosomal dominant, multisystemic and progressive disease, with multiple complications. These include high blood pressure, described in 6% of patients, mostly caused by renal artery stenosis, pheochromocytoma or coarctation of aorta. The hemangioblastoma, however, is the most characteristic lesion of VHL disease. In literature it has been reported association between VHL-NF1: both diseases are part of neurocutaneous syndromes and it is possible to hypothesise a common dysplastic origin.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the Fas apoptotic pathway. It can present with a wide range of clinical manifestations, including noninfectious nonmalignant lymphoadenopathy, splenomegaly and autoimmune pathology (frequently autoimmune citopenias). Revised diagnostic criteria allowed an improvement in its management. A 3-year-old boy was hospitalised for severe isolated thrombocytopenia (PLT 8000/mcl) and hemorragic syndrome. On physical examination, he had inguinal limphoadenopathy. His blood exams showed positivity for autoimmunity and normal lymphocyte population. Bone marrow aspirate revealed an immune throbocytopenia, so he started treatment with Immunoglobulins (Ig), with a good response. We performed an exeresis of his inguinal lymph node, increasing in dimensions, and found reactive follicular hyperplasia with dermatopathic aspects in absence of neoplasy. After one month, thrombocytopenia associated with neutropenia (N 800/mcl), positivity of direct and indirect Coombs test, anti-neutrophils antibodies negatives and splenomegaly on sonography. He assumed steroids for 2 weeks, with a good response. After 4 months, he presented again with thrombocytopenia, associated with emolitic autoimmune anaemia (Hb 5,2 g/dl) so he began therapy with Ig and steroids, with initial good response. Two months after stop therapy, new episode of thrombocytopenia, hemorragic syndrome and an increase of his splenomegaly. Therefore, we performed FAS-induced apoptosis test (negative) and researched double negative lymphocites that were positive (CD3+TCRαβ+CD4-CD8-:3,5%; CD19+CD27+:4,8%; CD3+CD25+/CD3+HLADR+ ratio:0,1%). He started therapy with mycophenolate mofetil and with Ig on demand. As we obteined a poor response, we shifted it to syrolimus, with progressive reduction of splenomegaly and increase of PLT. ALPS is a rare pathology that should be investigated in children with autoimmune citopenias and nonmalignant limphoproliferation. Its various clinical manifestations complicate diagnosis and treatment. First line treatment includes prednisone and Ig; for unresponsive patients mycophenolate mofetil and syrolimus are effective, the latter in children with refractory multilineage autoimmune cytopenias. Research over the past decades have increased our knowledge on its pathophysiology resulting in an improvement of its management. Its diagnosis is indeed crucial as ALPS may progress to lymphoma.

Background Neurofibromatosis Type 1 (NF1), a autosomal dominant disorder, which mainly involves Skin and nervous system: 15% of children with NF1 develops optic pathway gliomas (OPG), typically Astrocytomas pilocytic low grade, usually in the first decade of life. In one third of cases OPG occur with proptosis, visual impairment, early puberty or other disorders of hypothalamus-pituitary axis. According to current guidelines, children with NF1 should be screened frequently for visual examination and in case of visual impairment, brain MRI with the orbits analysis should performed. The current SIOP-LGG 2004 recommendations, in all cases of no-symptomatic, no-evolving glioma, provide clinical observation with close monitoring; chemotherapy is indicated only in presence of clinical signs and symptoms, or neuroimaging of progression. In the optic nerve tumours, surgery is reserved for patients with blindness, severe proptosis; chiasmatic tumours need surgery in case of exophytic tumours, with cystic component causing severe hydrocephalus or brain compression. patients and methods This is an observational study of 14 cases of OPG (5 males and 9 females) in patients with NF1, diagnosed from 1999 to 2015 c/o Paediatric Oncology Unit of our Department. We evaluated the clinical and radiological course and response to treatment of OPG. Results OPG were located exclusively to the optic nerves level in 43% of patients; 38% presented hypothalamus-optical-chiasmatic localization and 19% had chiasm or optic tracts involvment. The 57% of patients needed of chemotherapy according to the Protocol for Low Grade Glioma, cause of worsening of visual acuity, exophthalmoses or rapid increase of mass-size. The average age of chemotherapy start was 4.6 years (range 1.9 to 7 years). In only two cases there was marked reduction in the size of glioma, while in other cases the radiological picture was confirmed stationary at the stop-Therapy. Chemotherapy has allowed to stabilise the visual impairment, improving in 50% of cases the visual field. Conclusions Our data, accordingly with literature, confirmed that chemotherapeutic treatment for OPG is still unsatisfactory in most cases.

The association of genetic polymorphism in the estrogen receptor alpha (ERα) gene and risk for diseases including breast cancer (BC) has been the subject of great interest.Checking on women with high breast density after menopause, the frequency of the Pvull and Xbal polymorphisms of the ERα gene and the correlation between them and the known risk factors for breast cancer.Observational study with 308 women between 45 and 65 years old with high breast density, without hormonal therapy, menstruation for a year or more, breast and ovarian cancer history. It was characterized in clinical history and physical examination: menarche, menopause, parity, family history of BC, smoking, alcohol intake and body mass index.The allelic and genotypic frequencies for ERα-Pvull and Xbal: p = 43.99%; p = 56.01%; pp = 32.14%; Pp = 47.73% and PP = 20.13%; X = 41.56%; x = 58.44%; xx = 33.44%; Xx = 50.00% and XX = 16.56%, respectively. The most frequent risk factors for BC: menarche before 12 years old (35.38%), nulliparity or first child after 28 years old (41.66%), family history of BC (19.16%) and overweight/obesity (62.01%).Allelic and genotypic distribution similar to literature. The risk factors for BC were more prevalent in women with high breast density but without significant associations with these polymorphisms.

SUMMARY Female aging is a process that involves hypoestrogenism time, the individual impact on each woman, and what we can do as experts to reduce morbidity and provide quality of life. This natural process in the female life cycle has been of concern to women after menopause. Changes in different biophysical and psychosocial aspects, and their individual experiences, have repercussions on the lives of patients seeking specialized and multidisciplinary support to reduce the harmful effects of prolonged hypoestrogenism. Overweight and obesity, inadequate living habits and the presence of multi-morbidities cause damage to the quality of life and impact the functional capacity. Behavioral prescription and hormone therapy are among the treatments given to ease symptoms and reduce morbidity. A better understanding of these factors can help identify groups that require more care after menopause. RESUMO O envelhecimento feminino é um processo em que devemos correlacionar o tempo do hipoestrogenismo com o impacto individual em cada mulher e o que poderemos fazer, enquanto especialistas, para reduzir morbidades e proporcionar qualidade de vida. Esse processo natural no ciclo de vida da mulher tem sido motivo de preocupação das mulheres na pós-menopausa. As transformações nos diferentes aspectos biofísicos, psicossociais e em suas vivências individuais trazem repercussões na vida das pacientes, que buscam apoio especializado e multiprofissional para reduzir os efeitos deletérios do hipoestrogenismo prolongado. O sobrepeso e a obesidade, inadequados hábitos de vida e a presença de multimorbidades trazem prejuízos à qualidade de vida e impactam a capacidade funcional. A prescrição comportamental e a terapia hormonal são tratamentos indicados para amenizar os sintomas e reduzir morbidades. Assim, uma melhor compreensão desses fatores pode ajudar a identificar grupos propensos a cuidados na pós-menopausa.

SUMMARY Female aging is a process that involves hypoestrogenism time, the individual impact on each woman, and what we can do as experts to reduce morbidity and provide quality of life. This natural process in the female life cycle has been of concern to women after menopause. Changes in different biophysical and psychosocial aspects, and their individual experiences, have repercussions on the lives of patients seeking specialized and multidisciplinary support to reduce the harmful effects of prolonged hypoestrogenism. Overweight and obesity, inadequate living habits and the presence of multi-morbidities cause damage to the quality of life and impact the functional capacity. Behavioral prescription and hormone therapy are among the treatments given to ease symptoms and reduce morbidity. A better understanding of these factors can help identify groups that require more care after menopause.

Objective To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters. Study design We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS. Results From all patients, 30 (56.6%) were responders and 23 (43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH ( p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) ( p = 0.015). Conclusion In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects.

Emerging data reveal that oral estrogen therapy can increase clinic blood pressure (BP) in post-menopausal women; however, it is important to establish its effects on ambulatory BP, which is a better predictor for target-organ damage. Besides estrogen therapy, aerobic training is widely recommended for post-menopausal women, and it can decrease ambulatory BP levels. This study was designed to evaluate the effect of aerobic training and estrogen therapy on the ambulatory BP of post-menopausal women. Forty seven healthy hysterectomized women were randomly divided (in a double-blind manner) into 4 groups: placebo–control (PLA–CO = 12), estrogen therapy–control (ET–CO = 14), placebo–aerobic training (PLA–AT = 12), and estrogen therapy–aerobic training (ET–AT = 09). The ET groups received estradiol valerate (1 mg/day) and the AT groups performed cycle ergometer, 3×/week at moderate intensity. Hormonal status (blood analysis), maximal cardiopulmonary exercise test (VO2 peak) and ambulatory BP (24-h, daytime and nighttime) was evaluated before and 6 months after interventions. A significant increase in VO2 peak was observed only in women who participated in aerobic training groups (+4.6 ± 1.0 ml kg−1 min−1, P = 0.00). Follicle-stimulating hormone was a significant decreased in the ET groups (−18.65 ± 5.19 pg/ml, P = 0.00), and it was accompanied by an increase in circulating estrogen (56.1 ± 6.6 pg/ml). A significant increase was observed in the ET groups for daytime (P = 0.01) and nighttime systolic BP (P = 0.01), as well as nighttime diastolic BP (P = 0.02). However, daytime diastolic BP was increased only in the ET–CO group (+3.4 ± 1.2 mmHg, P = 0.04), and did not change in any other groups. No significant effect was found in ambulatory heart rate. In conclusion, aerobic training abolished the increase of daytime ambulatory BP induced by estrogen therapy in hysterectomized, healthy, normotensive and postmenopausal women.