Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sß°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

Clinical outcome of transfusions with extended red blood cell matching in ß-thalassemia patients: A single-center experience.

BACKGROUND: The development of alloantibodies may complicate the management of patients with ß-thalassemia. An extended antigenic matching may reduce the risk of alloimmunization. Our previous study showed that the introduction of molecular red blood cell (RBC) typing allows finding suitable blood units for multi-transfused patients. The aim of this study was to evaluate the benefit of RBC transfusion with extended antigenic match. MATERIALS AND METHODS: At the University of Campania "L. Vanvitelli", we selected ß-thalassemia major patients (age ≤23 years), without preformed alloantibodies. Data of patients receiving transfusion of leukoreduced RBC units for a period of one year with partial better match (PBM) including ABO, RhD, C/c, E/e, K/k antigens and consecutive one year with extended match (EM) including ABO, RhD, C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, S/s antigens, were compared. RESULTS: Eighteen patients, 8 males and 10 females with a mean age of 15.4 years (6.4 SD) received a mean number of 41.2 (6.0 SD) RBC units transfused with PBM and 41.8 (6.2 SD) with EM protocols. After two years of RBC transfusions with both antigen matching protocols, no new alloantibodies were developed in patients. No significant differences in Hb concentration and volume of RBC transfused were found between PBM and EM protocols. CONCLUSIONS: Thalassemia patients may benefit from receiving RBC transfusions based on extended antigen matching as demonstrated by the lack of new alloantibodies. However, our data show a high concordance between PBM and EM protocols considering pre-transfusion Hb, increment of Hb and volume of RBC transfused.

Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain.

Madelung disease : report of a case and review of the literature.

Madelung disease is a rare disorder characterized by the presence of multiple, symmetric, nonencapsulated fatty accumulations diffusely involving the cheeks, the neck, the upper trunk, the shoulder girdle area, and the upper extremities. The cause of this syndrome is unknown, but it has been associated with alcoholism in 60% to 90% of -patients. The long-term lipomatous deposits are often large and cosmetically deforming, and the upper aerodigestive tract and great veins may be compressed. We report the case of a man with MD, involving the cervical and upper dorsal -regions, who underwent surgical treatment at our Department.

Aneurysmatic disease in patients with Takayasu disease: a case review.

Takayasu disease is a non-specific inflammatory disease of the arterial system. Although various etiopathogenetic hypotheses have been formulated, its etiology remains unknown. The aorta and its main branches are predominantly involved in the disease, which is a form of panarteritis, starting with inflammation of the adventitia followed by involvement of the media and intima. It has been more frequently described in young oriental female patients. However, a worldwide distribution is being recognized. Arterial stenosis represents the most frequently diagnosed manifestation. Progression of the flogistic process may lead to stenosis of the aorta and supraaortic vessels, compromising arterial circulation to the brain and upper limbs. Aneurysm presentation may also rarely occur. Based on a recently treated case, the authors report on the clinical presentation, concomitant inflammatory diseases, current diagnostic methods, and management of this disease.

Surgical treatment of pericardial cyst through median sternotomy.

Pericardial cysts are an uncommon benign congenital anomaly in the middle mediastinum. They are thought to result from failure of fusion of one of the mesenchymal lacunae that form the pericardial sac. The authors present the case of a 77-year-old-man with a large pericardial cyst, treated by surgical resection trough a median sternotomy. They analyze the different diagnostic alternatives and the various management options in this pathology. In the reported case the authors used a surgical resection trough a median sternotomy, to facilitate the exposure of all of the cyst, extending around the great vessels area, and on the other side of the chest.

Cardiac transplant vasculopathy treated by percutaneous coronary intervention.

AIM: Cardiac transplant vasculopathy is a limit to long-term survival in heart transplantation (H-Tx) recipients. PTCA results in our H-Tx population were retrospectively analyzed. METHODS: From November 1985 to May 2004, 767 patients underwent heart transplantation. All patients received immunosuppressive therapy with cyclosporine or tacrolimus, azathioprine, steroids and mycophenolate mofetil. Lymphocyte was administrated by 3-7 days course of either rabbit antithymocyte globulins or anti-lymphocyte globulins or by a 14 days course of OKT3. Coronary angiograms were performed every year and more frequently if graft vasculopathy was already diagnosed or suspected. RESULTS: Fifty-two coronary artery lesions were treated during 42 percutaneous transluminal cardioangioplasty (PTCA)/stent procedures in 36 patients. Mean time since heart transplantation to PTCA was 80 +/- 27 months. Indication to PTCA was asymptomatic angiographic graft vasculopathy in 34 patients (94%) and acute myocardial infarction in 2 patients (6%). PTCA was performed on left anterior descending artery in 34 cases (65.4%), on circumflex artery in 10 cases (19.2%), on right coronary artery in 8 cases (15.4%). There were no procedure related deaths. None of the patients required emergency bypass surgery. Two patients had transient acute renal failure. Patient follow-up showed 10 deaths after 1 +/- 54 months from PTCA. Six died for progression of graft vasculopathy, three for cancer and one for gastrointestinal bleeding. Two patients underwent heart retransplantation after 20 and 107 months from the first procedure. Mean follow-up of the remaining patients is 78.3 +/- 50.3 months. CONCLUSION: PTCA may represent a reasonable treatment for graft vasculopathy in selected heart transplant recipients.

Body mass index and outcome after coronary artery bypass surgery.

AIM: Morbidity and mortality after surgical interventions are influenced by different preoperative factors. We investigated the impact of body mass index (BMI) on outcome after coronary artery bypass grafting (CABG). METHODS: A total of 4 749 CABG patients were divided into 4 groups: low BMI (or=35 kg/m(2), n=146). The incidence of severe perioperative complications (heart failure, renal failure or perioperative stroke), 30-day mortality, length of stay (LOS) and long-term survival were compared. A multivariate analysis with BMI, age, gender and Cleveland Clinic risk score as independent variables and 30-day mortality as dependent variable was performed. RESULTS: Compared to patients with normal BMI, low BMI patients had higher incidence of severe complications (12.5 vs 7.0%, P=0.039), higher 30-day mortality (6.2 vs 1.7 %, P=0.001) and inferior cumulative long-term survival (P=0.04). Patients with moderately increased BMI had longer LOS (10.8 vs 9.0 days, P=0.003) but no difference in incidence of severe complications or mortality. Patients with severely increased BMI had a higher incidence of severe complications (12.3 vs 7.0%, P=0.015, longer LOS (13.0 vs 9.0 days, P<0.001), but no significant difference in early or long-term mortality. Low but not high BMI was an independent predictor for 30-day mortality. CONCLUSIONS: The results suggest that low BMI is associated with increased morbidity and mortality after CABG. Overweight is associated with more postoperative complications and longer hospitalisation but not with an increased early or long-term mortality.

Reversible erythrocyte skeleton destabilization is modulated by beta-spectrin phosphorylation in childhood leukemia.

The erythrocyte skeleton plays an essential role in determining the shape and deformability of the red cell. Disruption of the interaction between components of the red cell membrane skeleton may cause loss of structural and functional integrity of the membrane. Several observations based on studies in vitro strongly suggest that phosphorylation may modify interactions between proteins, leading to a reduced affinity. In particular, increased phosphorylation of beta-spectrin decreases membrane mechanical stability. In order to investigate the presence of membrane protein defects we investigated the erythrocyte membrane protein composition and phosphorylation in 22 children with leukemia at diagnosis and during the remission phase. Sixteen children had acute lymphoblastic leukemia (ALL), three had chronic myeloid leukemia (CML) and three had acute myeloid leukemia (AML). Ten patients (eight ALL and two CML) displayed elliptocytosis and poikilocytosis, an increase of spectrin dimers (41.8 +/- 15.6) and an enhanced phosphorylation of beta-spectrin (108 +/- 15%) at diagnosis. These alterations disappeared during the remission phase. This is the first demonstration of a reversible erythrocyte membrane alteration in leukemia. Since the beta-spectrin phosphate sites are located near the C-terminal region and close to the head of the beta-chain that is involved in dimer-dimer interaction, we supposed that the beta-chain phosphorylation has an effect upon the interactions between spectrin dimers, ie the tetramerization process. The weakening of this process should be responsible for the presence of elliptocytes and poikilocytes as reported in hereditary elliptocytosis and pyropoikilocytosis.

Decreased band 3 anion transport activity and band 3 clusterization in congenital dyserythropoietic anemia type II.

Congenital dyserythropoietic anemia type II (CDA-II) is the most common form of inherited dyserythropoiesis. Erythroid precursor and red blood cells (RBCs) show characteristic morphological abnormalities. Biochemical studies have shown that this disease is associated with reduced glycosylation activity, which endows band 3 (anion transporter) with peculiar characteristics. The life span of RBCs may be shortened in patients with CDA-II, a phenomenon that has been ascribed to this membrane defect. We analyzed seven unrelated patients with CDA-II and five control subjects. In all of the CDA-II patients, erythrocytes presented a band 3 that was thinner than usual and also migrated slightly faster on SDS-PAGE. Analysis of anion transport function in CDA-II RBC samples demonstrated decreased anion exchange activity per band 3 molecule. Furthermore, we observed that the CDA-II RBCs contained larger amounts of aggregate band 3 than control erythrocytes. Aggregate band 3 has been reported to bind naturally occurring antibodies that mediate the phagocytic removal of RBCs. We provide evidence that both the phagocytic index (RBCs/macrophage) and the amount of membrane-bound immunoglobulin (IgG) are elevated in CDA-II erythrocytes. Our results suggest that the mild hemolysis observed in patients with CDA-II may be ascribed to clusterization of band 3, which leads to IgG binding and phagocytosis, and not to a secondary modification of the cytoskeletal structure of RBCs.

The use of intraoperative ultrasound for diagnosis and stadiation in pancreatic head neoformations.

UNLABELLED: The intraoperative staging of the pancreatic cancer is important to make a proper treatment. For this reason the intraoperative echography is playing an important role in the right treatment choice. The intraoperative echography, that can be performed with an open or laparoscopic probe, is used to confirm the preoperative diagnosis and assess the pancreatic cancer resecability. The intraoperative echography (IOUS) or laparoscopic intraoperative echography (LIOUS) are useful to identify the patients with a non resecable cancer and perform a faster neoadjuvant treatment. The LIOUS can also avoid an useless laparotomy. The aim of this study is to assess, both in our experience and in the cited literature, the concordance rate between the pancreatic cancer preoperative staging, performed with TC and MRI (when it is available), and intraoperative staging, performed with intraoperative laparotomic or laparoscopic echography. MATERIAL AND METHODS: We have analyzed the treatment management of 34 patients, who were candidate to major surgery for suspected pancreatic head cancer and who underwent to intraoperative LIOUS or IOUS staging from 2001 to 2012. RESULTS: LIOUS and IOUS have allowed to detect cases in which preoperative diagnosis, proved by CT and MRI, was not agreeing with intraoperative diagnosis (22 patients on 34, 64% discordance rate), avoiding the execution of a demolitive and uneseful surgery in order to guarantee the surveillance and life's quality of patients. CONCLUSION: We suggest to perform in every patients undergone to pancreatic surgery an intraoperative ultrasound exam, to detect unresecable and unpredicted lesions.

Long-term survival after curative resection for pancreatic ductal adenocarcinoma--Surgical treatment.

INTRODUCTION: Recent reports have demonstrated improvement in the 5-years serviva with resecate ductal adenocarcinoma. The aim of study is to determinate the factor influencing long-term survival after DCP. MATERIALS AND METHODS: We have critically reviewed a group of 85 patients how were admitted to our department with diagnosis of ductal adenocarcinoma of the head of pancreas between January 1974 and January 1998. RESULTS: Patients were stratified according to stage using TNM classification; in stage I 31 patients with 5 T1aN0M0 disease, 11 patients with T1bN0M0 and 15 patients T2N0M0 disease. By contrast, in stage III 54 patients with 48 patients T2N1M0 and 6 patients with T3N1M0. Tumour size was recorded for 72 patients with a median of 3.8 cm. The R1 dissection was performed in 67 patients. The R2 resection was performed in 18 patients. In our series we verified and analysed the histopathologic features of 5 patients with 15-years survival (5.8%). The features regard age, male or female, tumours size, stage and positive lymph node resection. DISCUSSION: We found a specifically subset of patients where the combination of prognostic factors, in particular, negative surgical margins R0, tumour size ≤ 30 mm and the absence of lymph node metastasis independently reduced the mortality indicating that earlier tumour detection and histologically curative resection are important factors contributing to long term survival and healing of ductal adenocarcinoma of the head of the pancreas.

Rare frequencey of point mutations for codon 12, 13 and 61 of ras gene in italian neuroblastoma.

Single point mutations of ras oncogenes are found in many tumors and contribute to the pathogenesis of the cancer. The product of the ras gene, p21 protein, was found expressed in several neuroblastoma tissues. However, the role of ras gene in this tumor has yet to be clarified. To contribute to the understanding of the ras activation, 79 fresh biopsies of neuroblastoma were studied to investigate the possibility that ras would be activated by point mutation. Analysis of H-ras and N-ras was performed by means of PCR and SSO, while K-ras mutations were detected by multiplex-ASPCR. None of the neuroblastomas examined showed H- or K-ras activation, while N-ras mutations were demonstrated in only three patients (3,7%). N-myc oncogene is amplified in a substantial number of patients with neuroblastoma. N-myc amplification was studied by Southern blot technique. N-myc amplification was demonstrated in 13.2% of patients less than 1 year of age at diagnosis and 23% of older children. Two of the patients (one stage I and one stage IVs) with N-ras mutation and without N-myc amplification had a good outcome, while the third (stage IVs) with N-myc amplification had a poor prognosis. These results suggest that ras activation is a rare event in both amplified and non-amplified neuroblastoma tumors and that N-ras activation was not involved in the clinical outcome of these patients. Moreover, our data suggest that p21 expression is induced by a post-transcriptional activation.

Recombinant erythropoietin therapy as an alternative to blood transfusions in infants with hereditary spherocytosis.

INTRODUCTION: In hereditary spherocytosis, erythropoiesis has been described as 'sluggish' during the first months of life. The lack of appropriate erythropoietic response to compensate for increased red cell destruction necessitates blood transfusions in 70-80% of hereditary spherocytosis-affected infants during their first year of life. After this period, less than 30% require regular transfusion support. This transient requirement for transfusion led us to wonder whether anemic hereditary spherocytosis infants, like anemic premature infants, could benefit from recombinant erythropoietin therapy (rHu-Epo). MATERIAL AND METHODS: In 16 hereditary spherocytosis infants (age range 16-119 days) with severe anemia, a compassionate open preliminary study was performed. rHu-Epo treatment (1000 IU/kg/week) was instituted together with iron supplementation. Hemoglobin values and reticulocyte counts were repeatedly assessed. RESULTS: In 13 out of 16 infants, prompt increases in reticulocyte counts were noted after the first week of treatment with 1000 IU/kg/week of rHu-Epo. During treatment with Epo these infants maintained clinically acceptable levels of hemoglobin and did not require blood transfusions. As the infants grew and began to mount an adequate erythropoietic response, the rHu-Epo dose could be tapered and the treatment could be discontinued before the age of nine months. CONCLUSION: Epo treatment in most hereditary spherocytosis infants appears to be effective in the management of anemia and could serve as a valuable alternative to packed RBC transfusions.

[Atrial septal aneurysm. Report of two clinical cases and review of the literature]. / Aneurisma del setto interatriale. Descrizione di due casi clinici e revisione della letteratura.

We report two cases of atrial septal aneurysm, one associated with paroxysmal supraventricular tachycardia, the second with atrial septal defect. In both cases there were verified some transitory ischemic attacks. Carotid ultrasonography excluded atherosclerosis lesions. Two-dimensional transthoracic echocardiography showed an atrial septal aneurysm which, in the second case, was associated with atrial septal defect as demonstrated by color Doppler. The therapy is discussed in the case of septal atrial aneurysm associated with transitory ischemic attack, anticoagulant therapy is indicated; in the other, surgical correction of the defect is necessary.

[Role of the subfascial endoscopic perforator vein surgery in the treatment of venous ulcers]. / Ruolo della interuzione sottofasciale delle vene perforanti per via endoscopica nella terapia delle ulcere flebostatiche.

BACKGROUND: Limbs phlebostatic ulcers are in many cases associated with perforator reflux veins often caused by post-thromboflebitis syndrome. The origin operation consisting in perforating vein interruption, described by Linton in 1938, allowed high quality exposition of these vessels and gave successful therapeutic results only affected by complications which prolonged hospitalisation. The most unfavorable prognostic factor was the need of performing an incision in skin sites affected by dermo-hypodermic degeneration induced by phlebopathy which inhibits post-surgery cicatrization. The therapeutic importance of reflux perforator vein interruption induced vascular surgeons to improve various procedures not affected by post-surgery complications and able to excise as much incontinent vessels as possible. METHODS: By video-surgery and new surgery tools nowadays available, the Subfascial Endoscopic Perforating Veins Surgery (SEPS) was established as a feasible and valuable method. At present, there are many surgical techniques differing from each other for the tools and the subneurotic compartement from which the perforating veins start. The results obtained from 45 SEPS procedures performed on 45 patients presenting lymphodermatosclerosis or venous ulcers caused by chronic venous insufficiency have been retrospectively evaluated. RESULTS: Thirty-six patients reached ulcer healing within 4 weeks after the operation; 7 ulcers healed over a 2 month time, while for 2 patients no clinical improvement has been recorded yet. CONCLUSIONS: SEPS is a valid alternative to the Linton procedure and provides remarkable advantages both in economic and clinical terms since it yields a more rapid lesions healing of small incisions which makes it one of the most minimally invasive surgical technique.

[Acquired deficiency of von Willebrand factor (wWF) associated with intestinal angiodysplasia. An unusual clinical case]. / Deficit acquisito di fattore di von Willebrand (FvW) associato ad angiodisplasia intestinale. Una insolita presentazione clinica.

A rare case of acquired von Willebrand's disease associated with intestinal angiodysplasia is described. The case is very interesting because it clinically mimicked an intestinal neoplasm.

[Non-invasive evaluation of the endothelial function using high-resolution B-mode ultrasonography]. / Valutazione non invasiva della funzione endoteliale mediante ultrasonografia B-mode ad alta risoluzione.

The vascular endothelium has a central role in regulating vasomotor tone, smooth muscle cell proliferation, platelet and leukocyte adhesion to the arterial wall, thrombosis and fibrinolysis. Disturbances of these endothelial functions have been suggested to be important in the early and advanced phases of atherosclerosis. The development of a simple, valid ultrasound-based method allowed to non-invasively evaluate endothelial function in a large number of individuals with traditional and non-traditional cardiovascular risk factors. The ultrasound technique measures changes in brachial artery diameter in response to an increase in blood flow (reactive hyperemia) and thus in shear stress, which causes endothelium-dependent dilation. This methodology is not yet perfect. The critical issues today involve the definition of "normal values", and standardized scanning and reading protocols to reduce variability.