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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.

Background Insulinomas are pancreatic endocrine tumors of rare incidence worldwide, the vast majority are of single occurrence and benign. These may not always present with the clear symptoms described in the literature and may be overlooked because their neuroglycopenic characteristics present in a fashion similar to some psychiatric conditions. Case report A 50-year-old Hispanic man referred severe psychomotor symptoms, described as anxiety, aggressiveness, agitation, weakness, diaphoresis, and decreased visual acuity. Laboratory testing performed during his last episode revealed increased insulin levels and C-peptide among other findings. Imaging, biopsy, and histopathologic analysis confirmed an insulinoma was the cause of the symptoms, proving the importance of ruling out organic causes of altered mental status prior to consideration of psychiatric disorders. Conclusion It is of critical importance to rule out organic causes of altered mental status prior to consideration of psychiatric disorders, as unusual diseases may be overlooked by physicians and be detrimental to the patient’s progress.

Background: The association between inflammatory bowel disease (IBD) and immune thrombocytopenia (ITP) is still uncertain. In this multicenter retrospective study, the coexistence of both diseases was investigated in children diagnosed from 1 January 2000 to 31 December 2019. Methods: Clinical characteristics of both IBD and ITP, onset of disorders, and patient’s response to treatment were collected through a structured form sent to 55 Italian pediatric referring centers for hematological disorders. Result: Centers responded to the survey and reported the coexistence of IBD and ITP in 14 children. The first diagnosis was ITP in 57.1% and IBD in 35.7% of patients: it was simultaneous in 7.1%. IBD was classified as ulcerative colitis (57.1%), Crohn disease (35.7%), and unclassified (7.1%). No therapy for IBD other than steroids had any effect on ITP course. Colectomy resulted in recovery from ITP in 1 of the 2 patients surgically treated. ITP was always mild but turned to be chronic in half of patients. Conclusions: In all patients, ITP was mild without any evident impact on IBD severity, but the incidence of chronic ITP seems to be higher than what is usually observed in the pediatric age group. Colectomy had unpredictable effects on ITP.

Background: Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression;furthermore, delays in treatment of patients with hematologic malignancies, especially those with acute leukemia planned for chemotherapy or transplantation, are associated with a risk of disease progression. To date, some societies recommend that chemotherapy should generally not be started until COVID-19 symptoms have completely resolved and viral testing becomes negative. However, implications of the aforementioned recommendations remain uncertain in routine clinical practice, and data on COVID-19 in patients with hematologic malignancies are still limited. Aims: We carried out a single-center analysis of acute leukemia inpatients who developed COVID-19 during the last year. Methods: Since February 2020 to February 2021, a total of 310 Hospitalizations,63 adult patients were admitted in our Center for treatment of hematologic malignancies. The indication for admission was acute myeloid leukemia (AML) in 50 (30%) patients, acute lymphoblastic leukemia (ALL) in4 (8%), lymphoma in 54 (33%), myeloma in4 (8%), other 31 (19%). Diagnosis of SARS-CoV-2 infection was based on virus detection by real-time polymerase chain reaction (SARS-CoV-2 E-gene RT-PCR) in respiratory tract specimens. Standard preventive measures for SARS-CoV-2 infection control were applied to all patients care, accordance with National disease control and prevention guidelines. Results: Ten (6%) patients tested positive for SARS-CoV-2 via PCR in a unique Covid-19 outbreak during hospitalization stay, and they were immediately transferred to Covid Infectious Unit. All these patients, were affected by Acute Leukemia (8 pts AML, 2 pts ALL ph negative), the majority of them was in peak of cytopenia at the Covid-19 infection time. Nine patients had been treated with intensive chemotherapy before SARS-CoV-2 confirmation. At SARS-CoV-2 diagnosis, only one patient had untreated, newly diagnosed AML;3 patients had refractory/relapsed AML. One patient was in complete remission with incomplete hematologic recovery (CRi). Deep vein thrombosis complicated by pulmonary embolism and interstitial pneumonia was observed in a patients despite anticoagulation and in thrombocytopenia. After SARS-CoV-2 infection, no leukemia-specific treatment was adjusted. Three patients (30%) died due to severe acute respiratory distress syndrome (ARDS) despite extracorporeal membrane oxygenation (ECMO) in deep aplasia, all of them was in refractory disease. Seven patients delayed in chemotherapy treatment for a media of 34 days;chemotherapy started until COVID-19 symptoms have completely resolved and two viral testing becomes negative. However, these patients are still alive and maintained their complete remission, remaining for long-time negative for SARS-CoV-2. One patient underwent to bone marrow transplantation Summary/Conclusion: Our findings support the vulnerability of patients with hematologic malignancies in the COVID-19 pandemic, and we reported a high COVID-19 infection mortality of 30%, in accordance with other hematological case series. However, deaths owing to Covid-19 were observed in patients in disease leukemia progression;furthermore, our recovered COVID-19 leukemia patients remained negative for SARSCoV- 2 after delivery of chemotherapy, and underwent to their following chemotherapy and allo-BMT program without any other complications.

Background Primary breast lymphoma (PBL) is an extremely rare neoplasm in children; by definition, it manifests in the breast without evidence of lymphoma elsewhere, except ipsilateral axillary nodes. Case presentation We report a case of a 15-year-old girl diagnosed with diffuse large B-cell lymphoma (DLBCL) of the right breast: the patient received chemotherapy and rituximab, achieving complete remission. A literature review revealed other 11 cases of pediatric PBL; it mainly affects female adolescents and can involve right and left breast equally. Different histologic subtypes have been described, arising from both B-cell and T-cell. Therapeutic approaches were very different, from chemotherapy to local treatment with surgery and/or radiotherapy. Conclusions Our case is the first in which rituximab was administered, suggesting to be a promising therapy in B-cell PBL, as already demonstrated in pediatric B-cell lymphoma from other sites. Further investigations are needed to identify prognostic factors and establish the most effective treatment.

Rasburicase is a recombinant urate oxidase enzyme indicated for tumor lysis syndrome, a potential life-threatening oncologic emergency that occurs most commonly during initial chemotherapy for hematological malignancies. As a result of the defects in the physiological antioxidant pathway, erythrocytes of patients with glucose-6-phosphate dehydrogenase deficiency are not protected against the oxidizing stress exerted by hydrogen peroxide generated with the administration of rasburicase. The authors report a 14-year-old patient, diagnosed with T-cell acute lymphoblastic leukemia, who developed methemoglobinemia and hemolytic anemia with low oxygen saturation after starting steroids, hyperhydratation, and rasburicase administration. The complications resolved with supportive therapy only.

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.

Properties of quantum light represent a tool for overcoming limits of classical optics. Several experiments have demonstrated this advantage ranging from quantum enhanced imaging to quantum illumination. In this work, experimental demonstration of quantum-enhanced resolution in confocal fluorescence microscopy will be presented. This is achieved by exploiting the non-classical photon statistics of fluorescence emission of single nitrogen-vacancy (NV) color centers in diamond. By developing a general model of super-resolution based on the direct sampling of the kth-order autocorrelation function of the photoluminescence signal, we show the possibility to resolve, in principle, arbitrarily close emitting centers. Finally, possible applications of NV-based fluorescent nanodiamonds in biosensing and future developments will be presented.

Background Autoimmune neutropenia is a chronic reduction of absolute neutrophil below the threshold for age, due to peripheral destruction by specific antibodies (AaN). "Primary autoimmune neutropenia" (pAN) usually appears in early infancy and generally resolve within 18-24 months, while "Secondary autoimmune Neutropenia" (sAN) rises later in life and is usually accompanied by autoimmune features. Very few descriptions on the topic are available in the literature. Aim of the study: to describe from a clinical and immunological point of view a cohort of subjects affected with sAN included registered in the Italian Neutropenia Registry (INR) and to compare these data with those from subjects diagnosed with pAN still in the INR . Patient and methods Subjects with neutropenia and positivity of AaN lasting for more than 2 years in subjects older than 5 years of life ( up to 18) or patients affected with neutropenia (plus AaN) associated with autoimmune features registered in the INR from 2005 to 2018 were considered eligible for the present study. Antibodies against neutrophils were always detected throught indirect test . Results: Data from 40 patients affected with sAN (26 females, 65%) were collected. Median age at diagnosis was of 11.6 years (0-21.558mo) with a median follow up of 17 months (0-159mo). The degree of Neutropenia was mild in 12.5%(5/40), moderate in 35% (14/40) and severe in 52.5% (21/40) Neutropenia was diagnosed by chance in half of the cohort and in only 10% (4/40) (10%) definitively resolved . Neutropenia coexisted with leucopenia in almost all the of subjects (36/40, 88%), and moreover, autoimmune haemolytic anemia and thrombocytopenia was concomitant to neutropenia in 12% (5/40) and 32.5% in (13/40) of cases respectively. As for clinical history, 15% (6/40) subjects (15%) were completely asymptomatic , while the remaining 85% (36/40) (85%) had clinical signs of infections and/or autoimmunity features . Infections were documented in 60% (24/40) (60%) of patients. Severe infections namely sepsis , meningitis, pneumonia, osteomyielitis and broad absesses/flemmons were identified in 21% (5/24) of the group. Other type of infections are listed Figure 1A. Apparently there was no correlation between severity of infections and degree of neutropenia ( p=0.2 Fisher' exact test) Autoimmune features and/or autoimmunity markers were present in 30/40 (75% ) of the entire cohort . Thyroiditis and artralgia/arthritis were the most common signs which accounted both for 17,5% of the total episodes. Positivity of ANA and Direct antibodies test ( DAT) were showed in 42% and 29% of cases respectively. (Fig 1B, 1C) As for immunological characteristic 37% (12/32) of the studied subjects were frankly lymphocytopenic, 19% (6/32) had borderline values , while the remaining 44% (14/32) had normal lymphocytes subclasses. In terms of frequency of sub-classes depletion CD19 + and NK were the most frequently decreased subsets. ( Fig 1D) . Dosage of serum immunoglobulin (IgG, IgM and IgA) were shown for all three classes were abnormal (either increased or diminished) in 74% (28/38) of patients (Fig 1D). Mutation analysis performed by Next Generation Sequencing in 16/40 subjects and pathogenic variants of : TACI, TINF 2, CASP 8, CASP 10, PI3K, CARD 11 genes were identified in 4/16 (25%). As for treatment, in 25 % of cases needed Granulocyte-Colony Stimulating Factor to control infections. Rapamicin, micophenolate mofetil, steroids, intravenous immunoglobulin were necessary in 25% (10/40) of patients cases, being (4 of them were already treated on with G-CSF) Comparison with a group of 236 pAN patients of the INR showed that sAN were older at diagnosis (P Conclusions This registry study describes the clinical phenotype of sAN appearing in childhood and by comparative analysis shows that sAN substantially differs from pAN. sAN indeed appears an epiphenomenon of a complex immunological disturbances rather than a disease itself. Occasionally mutations of genes of immunodeficiency/disimmunity can be demonstrated Disclosures No relevant conflicts of interest to declare.

We report a female patient with asymptomatic cor triatriatum sinister, associated with 4q34.3 deletion. Her child, carrying the same imbalance, suffers from tetralogy of Fallot. To the best of our knowledge, this is the first reported case of cor triatriatum associated with deletion of the long arm of the chromosome 4; furthermore, the majority of patients with chromosome 4 long arm syndrome have de novo deletions and only few familial cases have been reported so far.

Background: Lipid peroxidation and oxidative stress are enhanced in peripheral blood mononuclear cells (PBMCs) from hemodialysis (HD) patients because of upregulation of the 5-lipoxygenase pathway of the arachidonate cascade. 5-Lipoxygenase activity is specifically inhibited by vitamin E both in vitro and in vivo regardless of its administration route. Methods: The effect of arachidonate cascade enzymes and vitamin E on oxidative stress and apoptosis was investigated in PBMCs from 16 maintenance HD patients treated for at least 6 months with cuprammonium rayon membranes in a two-step crossover study: after a 4-week treatment with vitamin E-coated cuprammonium rayon membranes and again after a 4-week treatment with oral vitamin E. Control PBMCs were obtained from 16 healthy volunteers. Results: Membrane lipoperoxidation, cellular luminescence, membrane fluidity, and leukotriene B 4 content were significantly greater in PBMCs from HD patients; lipoxygenase was upregulated, but prostaglandin H synthase (PHS) was not affected. Regardless of administration route, vitamin E partially controlled lipid peroxidation and oxidative stress through direct inhibition of 5-lipoxygenase. Cultured PBMCs from HD patients showed a significant increase in apoptotic cells compared with controls. Vitamin E markedly reduced cell luminescence, membrane fluidity, and apoptosis, whereas the PHS inhibitor indomethacin was ineffective. Similar results were obtained with control PBMCs induced to apoptosis by hydrogen peroxide. Conclusion: Reported data suggest that the 5-lipoxygenase branch of the arachidonate cascade is only responsible for membrane peroxidation, oxidative stress, and apoptosis of PBMCs of HD patients, and administration of vitamin E may be helpful in the control of oxidative stress-related disease in these subjects. © 2002 by the National Kidney Foundation, Inc.

Background and aims Complications of inflammatory bowel disease (IBD) may involve gastro-intestinal system and several other organs. Extraintestinal manifestations (EIMs) are reported in about one third of adults with IBD and they may be related or not to disease activity, or adverse effects related to therapy (ADR, Adverse Drug Reactions). In paediatric patients EIMs are yet poorly understood, with few published data. Here we describe local complications and EIMs in our paediatric series of IBD patients. Methods Five paediatric patients (age 10–18) with complicated IBD were enrolled. Diagnosis of IBD was obtained by integrating clinical data, laboratory tests, imaging studies (Magnetic Resonance Enterography) and endoscopy. All underwent protocol therapy with azathioprine and mesalazine. Results 80% of patients (4/5) had a Crohn’s disease, 20% (1/5) an indeterminate colitis. 4 patients (80%) were females. Local complications reported were 2 cases of intestinal occlusion which required long hospitalisation, antibiotic therapy and total parenteral nutrition, and 1 case of bowel fistulization and formation of abscess treated with combined antibiotic and biological therapy. The most frequent EIMs were ADR: 2 cases of recurrent hypertransaminasemia due to mesalazine, 2 asymptomatic pancreatitis by azathioprine, 1 hypercortisolism with osteopenia, hypertrichosis and round face. All the reported ADR resolved spontaneously stopping the drug administration. The remaining observed EIMs were 1 case of Sweet’s syndrome with spontaneous resolution and 1 case of sideropenic anaemia. Conclusions In our patients local complications of IBD were severe and required hospitalisation with aggressive therapy; ADR were mostly due to reversible effects of treatment. This emphasises the need for more targeted therapies in children.