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.

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.

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.

The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption.

Recent studies suggest a role for the endocannabinoid/endovanilloid anandamide in the regulation of bone resorption/formation balance in mice. Here, we examined the co-expression of the transient receptor potential vanilloid type 1 (TRPV1) and the cannabinoid CB1/CB2 receptors together with N-acylphosphatidylethanolamine-hydrolizing phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), the two enzymes responsible of the synthesis and catabolism of anandamide respectively, in human osteoclasts. Co-expression of TRPV1, CB1/CB2, NAPE-PLD and FAAH was found in both human osteoclast cultures and in native osteoclasts from human bone biopsies. Moreover, agonist-evoked calcium entry indicated that the TRPV1 receptor is functionally active in vitro. Consistently, biomolecular and functional experiments showed that resiniferatoxin (RTX), a selective TRPV1 receptor agonist, increased the expression and the activity of TRAP and cathepsin K, two specific osteoclast biomarkers. The evidence that cannabinoid and vanilloid receptors are co-expressed in human osteoclasts suggests that they might cross-talk to modulate the intrinsic balance of bone mineralization and resorption by different actions of anandamide through TRPV1 and cannabinoid receptors. The presence of the endocannabinoid/endovanilloid proteins in human osteoclasts will likely have implications for the management of bone demineralization associated syndrome (i. e. osteoporosis).

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.

Hepatitis C virus carriers with persistently normal ALT levels: biological peculiarities and update of the natural history of liver disease at 10 years.

Some chronic hepatitis C (CHC) patients exhibit persistently normal alanine aminotransferase (ALT) levels (PNAL). Patients with PNAL experience significantly milder disease. In order to understand the differences between CHC patients with elevated ALT levels compared with those with PNAL better, we compared epidemiological, immunological and histological findings, in particular, the value of proliferating hepatocyte activity (PCNA) between the two groups of patients. We studied 40 chronic hepatitis C virus (HCV) carriers with increased ALT who underwent liver biopsy for histological diagnosis and determination of clinical prognosis, and 24 PNAL patients under follow-up for 10 years. Immunological response to different HCV genomic epitopes was tested in both the control group and in PNAL subjects. PCNA values from liver specimens of all patients as well as liver biopsies of PNAL patients at time points 0 and 5 years were calculated according to Hall et al.Age, sex and body mass index (BMI) were not significantly different between the two groups. The median liver histology stage was significantly higher in HCV carriers vs the PNAL group (2.5, range = 2-6 vs 1.5, range = 1-2; P < 0.01). Among PNAL patients, histological stage was not statistically different at the three time points considered. Interferon (IFN)-gamma production was comparable in the two groups. PCNA was significantly higher in the group with elevated ALT levels vs the PNAL group (8%, range = 4-15%vs 5% range = 3-8%; P < 0.05) and no statistically significant differences were found in PNAL patients at time points 0, 5 and 10 years. This study confirms that progression to cirrhosis is slow or absent in PNAL patients after 10 years of follow-up. Accordingly, the hepatic proliferative activity index is low and seems to be stable over time.

[Idiopathic and secondary osteoporosis in childhood]. / L'osteoporosi primitiva e secondaria in età pediatrica.

Osteoporosis is a common disease characterized by reduced bone mass, with a consequent increase in bone fragility and susceptibility to fracture risk. Bone mineral density (BMD) measurement is used to make the diagnosis of osteoporosis prior to incident fracture, and to predict fracture risk. BMD is determined by the peak bone mass achieved, and the rate and timing of subsequent bone loss. Dual-energy X-ray absorptiometry (DEXA) is the most popular and effective method utilized for osteoporosis screening. Bone disease is a side effect of concern regarding chronic glucocorticoid (GC) administration. Most GC-treated patients exhibit a process of bone loss, frequently leading to osteoporosis, with increased fracture risk, especially in spinal vertebrae. Osteogenesis imperfecta is an inherited and generalized connective tissue disorder characterized mainly by bone fragility. Idiopathic osteoporosis of childhood or adolescence without blue sclerae and other stigmata of osteogenesis imperfecta is occasionally observed and sometimes more than one sib is affected. Beta-thalassemia major is associated with significant bone disease. The etiology of the bone disease is still debatable, many factors can adversely affect bone accretion in thalassemic patients. These include delayed puberty, bone marrow expansion, the deleterious effects of desferrioxamine, iron overload and genetic factors. Current treatment alternatives of osteoporosis include bisphosphonates, calcitonin, and selective estrogen receptor modulators.

[Inherited disorders of bilirubin metabolism]. / Disordini ereditari del metabolismo della bilirubina.

Jaundice in an infant or older child may reflect accumulation of either unconjugated or conjugated bilirubin and could be related to inherited bilirubin disorders. Three grades of inherited unconjugated hyperbilirubinemia are recognised in humans. This spectrum of disorders is distinguished primarily on the basis of the plasma bilirubin level, the response to phenobarbital administration, and the presence or absence of bilirubin glucoronides in bile. The enzyme responsible for the conjugation of bilirubin is the bilirubin uridine-diphosphate-glucuronosyltransferase (UGT). Mutations in the gene encoding bilirubin-UGT (UGT1A1), lead to complete or partial inactivation of the enzyme causing the rare autosomal recessively inherited conditions, Crigler-Najjar syndrome type 1 (CN-1) and type 2 (CN-2). Gilbert syndrome (GS) is due to an insertional mutation at homozygous state of the TATAA element (seven TA repeats) of UGT1A1 producing a reduced level of expression of the gene. The association of GS with haemolytic anemias, e.g., Hereditary Spherocytosis (HS) or Congenital Dyserythropoietic Anemia type 2 (CDA 2), increase the hyperbilirubinemia level and the risk of cholelithiasis. Forms of chronic conjugated hyperbilirubinemia are Dubin-Johnson syndrome, Rotor syndrome, Alagille syndrome or arteriohepatic dysplasia, Wilson disease or hepatolenticular degeneration. Liver or liver cell transplantation is the therapy in some cases.

Minimally invasive closure of patent foramen ovale through port-access surgery.

We present here our experience of patent foramen ovale closure through a mini-invasive surgical technique. With the new surgical platform termed Heartport System, it is possible to install extra-corporeal circulation and to obtain cardioplegic arrest of the heart with endovascular techniques. This allows the operation of closure to be entirely performed through a micro-thoracotomy (Port-access surgery) in the right 4th intercostal space. Sixty-one patients underwent this surgical correction and seventeen of them (26%) had a diagnosis of patent foramen ovale, 12 with an history of cerebrovascular accidents. They are all alive and well after a mean follow-up of 16 months, with no recurrence of the inter-atrial communication and free from new neurological events. The post-operative course was uneventful with patients discharged on postoperative day 4. This technique shows a 100% efficacy, minimise surgical trauma, allows a quick recovery and offers excellent cosmetic results with no scarring. We believe that this procedure must be regarded as the "golden standard" for the closure of atrial septal defects

[Intraoperative cholangiography in videolaparoscopic cholecystectomy: indications, advantages, and limitations]. / Colangiografia intraoperatoria in corso di colecistectomia videolaparoscopica: indicazioni, vantaggi, limiti.

Consensus doesn't exist about the intraoperative cholangiography specially if is need in every one laparoscopic cholecystectomy either exclusively in case of anatomical doubts or suspect of injures or stones of the common duct. We have considered 450 patient subjected to laparoscopic cholecystectomy during 1992-2000. Patients suspicious to be affected by common duct lithiasis (28 cases) are subjected to ERCP with cleaning of the biliary tree. In 18 patients (4%) it has been necessary the laparotomic conversion; 176 patients (39%) have been subjected to intraoperative cholangiography, selected on anatomical regional disposition or anamnesis and biochemical and instrumental results (history of jaundice or gallstones pancreatitis, abnormal serum level of the biliary stasis biochemistry, common bile duct major of 8 mm, michrolitiasis of the gallbladder). In 7 cases (4%) we have discovered common bile duct stones. We don't attempt intraoperative cholangiography in every one laparoscopic cholecystectomy, but only in cases where we suspect presence of common bile duct stones either iatrogenic injuries or when we retain it necessary to clarify the regional anatomy. Unlikely just in patients where would be more useful, causes major risk of intra- and post-operative complications, it is very difficult, often impossible, to attempt the intraoperative cholangiography. Routinary employing of the intraoperative cholangiography could be useful just for a little number of patients, while selective employing reduce 60% the X-ray. Collaboration with the radiologist is able to reduce the mistaken on the interpretation of the radiograms.

[Surgical complications following pancreaticoduodenectomy: results of a single center experience]. / Le complicanze chirurgiche post-duodenocefalopancreasectomia: risultati di una esperienza monocentrica.

Pancreaticoduodenectomy represents the only therapeutic option for cefalo-pancreatic and periampullary cancers. Surgical and anaesthesiological techniques development over the last twenty years has granted an operative mortality decrease. However, surgical morbidity is still high, with an incidence of 30-50%. A 20 year experience of a single Centre is examined retrospectively: 121 patients underwent pancreatic resection with radical intent. Type of operation or re-operation, operative mortality within 30 days, general and surgical morbidity, postoperative hospital stay were analysed. Average recovery time was 24 days (range 12-65); operative mortality was 5.8% (7/121); general morbidity, including medical and surgical complications, was observed in 47 patients (38.8%). Pancreatic fistula occurred in 16 patients (13.2%); ten of these underwent a second operation. Patients who underwent pancreaticoduodenctomy were divided as follows: 76 pts. received a pylours-preserving pancreaticoduodenectomy and 45 a Whipple's resection. Neither surgical complications incidence nor mortality rate were significantly different between the two groups. Postoperative complications following pancreaticoduodenectomy are still frequent and severe. In particular, pancreatic fistula represents the most relevant complication following pancreaticoduodenectomy. The Authors suggest that standard and meticulous surgical procedures together with continued efforts to improve postoperative follow-up, support early detection of complications and improvement of results in most patients.