An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked recessive lysosomal storage disorder due to a mutation in the lysosomal enzyme iduronate-2-sulfatase (IDS) gene. IDS deficiency leads to a progressive, multisystem accumulation of glycosaminoglycans (GAGs) and results in central nervous system (CNS) manifestations in the severe form. We developed up to clinical readiness a new hematopoietic stem cell (HSC) gene therapy approach for MPS II that benefits from a novel highly effective transduction protocol. We first provided proof of concept of efficacy of our approach aimed at enhanced IDS enzyme delivery to the CNS in a murine study of immediate translational value, employing a lentiviral vector (LV) encoding a codon-optimized human IDS cDNA. Then the therapeutic LV was tested for its ability to efficiently and safely transduce bona fide human HSCs in clinically relevant conditions according to a standard vs. a novel protocol that demonstrated superior ability to transduce bona fide long-term repopulating HSCs. Overall, these results provide strong proof of concept for the clinical translation of this approach for the treatment of Hunter syndrome.

Systemic Fusariosis: A Rare Complication in Children with Acute Lymphoblastic Leukemia.

Fusarium species are ubiquitous pathogens causing opportunistic infections in immunocompromised patients. Clinical presentation depends on a host's immunity and can be localized or disseminated. Since there are few reports of disseminated fusariosis in children, we described an unusual case of Fusarium solani infection in a 9-year-old child with acute lymphoblastic leukemia (ALL). This patient presented a deep wound in the elbow at diagnosis. During the induction phase of chemotherapy, he developed multiple skin lesions and severe pneumonia; Fusarium solani was cultured from the skin lesions. He was treated with a high dose of liposomal amphotericin B, followed by voriconazole. Starting from this peculiar case, we collected all patients with acute leukemia affected by Fusarium infection, treated in the pediatric Onco-Hematology Division of Padua University Hospital during the last 20 years. We identified another six cases: all these patients were affected by acute myeloid leukemia (AML) and five of them presented a relapsed/refractory disease. Two out of seven patients died because of infection; five patients recovered from infection, but three out of seven died because of leukemia. Skin lesions in immunocompromised patients should rise the suspicion of disseminated fusariosis. Furthermore, considering the emergence of filamentous fungi in immunocompromised patients, we all should be aware of Fusarium infection, reminding us that the diagnosis is important to cure the infection.

Nontraumatic tension pneumopericardium in nonventilated pediatric patients: a review.

BACKGROUND AND AIMS: Pneumopericardium is a rare air leak syndrome caused by the abnormal presence of air in the pericardial sac, with a high risk of morbidity and mortality. It is clinically divided into nontension and tension pneumopericardium, with the latter resulting in a decreased cardiac output and circulatory failure. There are limited data regarding nontraumatic pneumopericardium in nonventilated pediatric patients. Therefore, we aimed to describe a case of tension pneumopericardium and review the available literature. METHODS: Case report and literature review of nontraumatic pneumopericardium in nonventilated pediatric patients. RESULTS: A 2-month-old infant developed cardiac tamponade secondary to tension pneumopericardium 11 days after cardiac surgery promptly resolved with pericardium drainage. We reviewed the literature on this topic and retrieved 50 cases, of which 72% were nontension whereas a minority were tension pneumopericardium (28%). Patients with tension pneumopericardium were mostly neonates (35.7% vs 22.2%), presented with an isolated air leak (64.3% vs 36.1%), and had a history of surgery (28.6% vs 8.3%) or hematological disease (28.6% vs 11.1%). In all nontension cases, treatment was conservative, whilst in all other cases, pericardiocentesis/pericardium drainage was carried out. There was a high survival rate (86.0%), which was lower in patients with tension pneumopericardium (71.4% vs 91.6%). CONCLUSIONS: Pneumopericardium is a rare condition with a higher mortality rate in patients with tension pneumopericardium, which requires immediate diagnosis and treatment. In nonventilated patients, tension pneumopericardium occurred more frequently in neonates, as an isolated air leak, and in those with a history of surgery or hematological disease.

Use of Scrambler Therapy in Acute Paediatric Pain: A Case Report and Review of the Literature.

We report our clinical experience on the effect of Scrambler Therapy (ST) for a child with acute mixed pain refractory to pharmacological treatment. ST, recently proposed as an alternative treatment for chronic neuropathic pain in adults, is a noninvasive approach to relieve pain, by changing pain perception at brain level. It is safe and has no side effects. Further research is needed to assess its efficacy for acute pain and for paediatric population.