Disseminated Mycobacterium scrofulaceum infection in a child with interferon-γ receptor 1 deficiency

Summary Disseminated disease caused by non-tuberculous, environmental mycobacteria (EM) reflects impaired host immunity. Disseminated disease caused by Mycobacterium scrofulaceum has primarily been reported in patients with AIDS. Moreover, observing M. scrofulaceum as the agent of localized disease in childhood has become increasingly rare. We report the first case of disseminated disease caused by M. scrofulaceum in a child with inherited interferon-γ receptor 1 (IFN-γR1) complete deficiency. As in this case, mycobacterial bone infections in IFN-γR1 deficiency can sometimes mimic the clinical picture of chronic recurrent multifocal osteomyelitis

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine

Management of chronic hepatitis C in childhood: The impact of therapy in the clinical practice during the first 2 decades

Background and aim: Treatment of chronic hepatitis C in children is controversial and its role in the clinical practice is unknown. We retrospectively investigated the impact of treatment in a large cohort of children with chronic hepatitis C over the past 20years. Methods: 376 hepatitis C virus RNApositive children were recruited consecutively in five Italian centres since 1990and followed for1–17years. Results: 86 (23%)subjects were treated: 73 with recombinant interferon alone and 13 with pegylated-interferon and ribavirin. Sustained clearance of hepatitis C virus RNA was observed in 25%of the former, in 92%of the latter and in 9% of untreated cases(p < 0.001). Loss of viraemia was recorded in all children with genotype2–3 and in 6of7 with hepatitis C virus genotype 1 treated with combination therapy.At last evaluation 45% of patients were young adults and 15%had cleared viraemia. Overall, 152 (40%)were putative candidates to therapy. Conclusions: Few Italian children with chronic hepatitis C have been treated in the past 20years.The poor propensity to spontaneous clearance of viraemia and the efficacy of ombination therapy should encourage to consider treatment in attempt to shorten the duration of viral replication

Persistence of elevated aminotransferases in Wilson's despite adeguate therapy.

Wilson's disease (WD) is characterized by a dramatic build-up of intracellular hepatic copper with subsequent hepatic and neurological abnormalities.1, 2 Prompt recognition of WD is crucial, because if not treated, the disease is fatal.2, 3 Most childhood cases of WD present with liver disease that mimics various liver disorders, while the typical neurological signs are usually absent. Hypertransaminasemia may be the only altered laboratory sign in early WD. Histological evidence of severe liver disease may occur in children with isolated hypertransaminasemia.4, 5 The response of serum transaminase levels to penicillamine and zinc treatment in WD is poorly understood, because the children with WD in earlier studies had a relatively advanced disease, and treatment efficacy was evaluated from parameters (i.e., jaundice, ascites, and neurological symptoms) other than serum transaminases.6–

Persistence of elevated aminotransferases in Wilson's disease despite adequate therapy

The persistence of elevated aminotransferases in Wilson's disease despite adequate therapy is discusse

Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period

Background/Aims: To evaluate the epidemiological profile of Italian children with hepatitis C virus (HCV) infection over a 15-year period. Methods: Fifteen tertiary care centers, belonging to a national Observatory established in 1998, retrospectively/prospectively recruited 806 consecutive HCV-infected, otherwise healthy, children seen from 1990 to 2004. Results: Seven hundred and sixty four were Italian and 42 from foreign countries. Newly-diagnosed cases declined from 332 in 1995-1999 to 196 in 2000-2004, while the proportion of foreign children rose from 3% to 13%. Transfusion-transmitted infection disappeared after 1992. Maternal infection (with drug abuse in 63% of cases in the North) has become the most important mode of HCV diffusion throughout Italy and the exclusive source for all children infected in 2000-2004. The prevalence of HCV genotypes 3 and 4 increased and that of genotype 1b decreased significantly (p < 0.02). Male/female ratio was significantly (p < 0.001) lower among vertically infected (0.6) than in transfused children (1.3). Conclusions: The number of children with newly-diagnosed HCV infection is declining in Italy and most post-transfusion cases are now young adults. Thus foreign children could significantly contribute to the reservoir of pediatric infection in years to come. New infections result from maternal transmission and seem to privilege females and genotypes 3 and 4. © 2007 European Association for the Study of the Liver

The Canine copper toxicosis gene <i>MURR1</i> is not implicated in the pathogenesis of Wilson disease

Background It has recently been demonstrated that the Wilson disease (WD) protein directly interacts with the human homolog of the MURR1 protein in vitro and in vivo, and that this interaction is specific for the copper transporter. The aim of the present study was to clarify the role of MURR1 in the pathogenesis of WD as well as in other WD-like disorders of hepatic copper metabolism of unknown origin. Methods Using the single-strand conformation polymorphism (SSCP) method followed by sequencing, we analyzed the 5′ untranslated region (UTR) and three exons of the MURR1 gene in three groups of patients: 19 wd patients in whom no mutations were detected in the ATP7B gene, 53 wd patients in whom only one mutation in the ATP7B gene was found, and 34 patients in whom clinical and laboratory data suggested a WD-like disorder of hepatic copper metabolism of unknown origin. Results We  detected in these patients six rare nucleotide substitutions, namely one splice-site consensus sequence and one missense and four silent nucleotide substitutions. All substitutions except one were found in the heterozygous state. No difference in the frequencies of the various substitutions was observed between patients and controls. Conclusions These data suggest that the MURR1 gene and its protein product are unlikely to play a primary role in the pathogenesis of Wilson disease. More extensive studies with larger numbers of clinically homogeneous patients should be carried out to establish whether nucleotide alterations in the MURR1 gene may have a role in causing WD or WD-like disorders or act as modifying factors in the phenotype variability in WD.</br