Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency.

OBJECTIVES: Sebelipase alfa is approved for treatment of lysosomal acid lipase deficiency (LAL-D). This single-arm, open-label study (NCT02112994) evaluated sebelipase alfa efficacy and safety in patients with LAL-D. METHODS: Patients >8 months of age diagnosed with LAL-D received sebelipase alfa 1.0 mg/kg by intravenous infusion every other week (qow) for up to 144 weeks. Dose escalation to 3.0 mg/kg qow and subsequently to 3.0 mg/kg weekly was permitted, per protocol; dose reductions for tolerability were permitted to 0.35 mg/kg qow. Descriptive statistical analyses were conducted. RESULTS: Thirty-one patients were enrolled and treated. Baseline median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were 63.5 and 65.5 U/L, respectively. Twenty-eight patients completed 96 weeks of treatment, and 25 continued into the extended treatment period; 19 completed 144 weeks. From baseline to week 144, median ALT and AST levels changed by -42.0 and -22.0 U/L, respectively, median liver and spleen volumes changed from 1.4 to 1.3 and from 2.6 to 2.3 multiples of normal, respectively, median low-density lipoprotein cholesterol levels decreased by 52.6 mg/dL, and median high-density lipoprotein cholesterol increased by 9.8 mg/dL. Liver biopsies showed mostly improved or stable histopathology at 48 and 96 weeks versus baseline. Infusion-associated reactions were mild (n = 1) or moderate (n = 2). One patient (a candidate for liver transplant at baseline) discontinued treatment because of liver transplant (unrelated to treatment). Two patients tested positive for nonneutralizing, anti-drug antibodies on 1 occasion each. CONCLUSION: Sebelipase alfa was well tolerated and resulted in sustained improvements in liver and lipid parameters.

Inference from the analysis of genetic structure of Helicobacter pylori strains isolates from two paediatric patients with recurrent infection.

BACKGROUND: Helicobacter pylori recurrence after successful eradication is an important problem. Children are particularly vulnerable to reinfection, by intrafamilial transmission which facilitates the acquisition or recombination of new genetic information by this bacterium. We investigated the evolutionary dynamics of 80 H. pylori strains isolated from two paediatric patients with recurrent infection (recrudescence and reinfection). RESULTS: We characterized the virulence genes vacA (s1, m1, s2, and m2), cagA, cagE, and babA2 and performed multilocus sequence typing (MLST) on 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, and yphC) to infer the evolutionary dynamics of the H. pylori strains through phylogenetic and genealogic inference analyses, genetic diversity analysis and the exploration of recombination events during recurrent infections. The virulence genotype vacAs1m1/cagA+/cagE+/babA2 was present at a high frequency, as were the EPIYA motifs EPIYA-A, -B and -C. Furthermore, the housekeeping genes of the H. pylori strains exhibited high genetic variation, comprising 26 new alleles and 17 new Sequence Type (ST). In addition, the hpEurope (76.5%) and hspWAfrica (23.5%) populations predominated among the paediatric strains. All strains, regardless of their ancestral affiliation, harboured western EPIYA motifs. CONCLUSIONS: This study provides evidence of the evolutionary dynamics of the H. pylori strains in two paediatric patients during recrudescence and reinfection events. In particular, our study shows that the strains changed during these events, as evidenced by the presence of different STs that emerged before and after treatment; these changes may be due to the accumulation of mutations and recombination events during the diversification process and recolonization of the patients by different genotypes.

Pancreatitis aguda / Acute pancreatitis

La sospecha de pancreatitis aguda debe surgir cuando existe dolor abdominal e intolerancia a la vía oral, sobre todo en un paciente que ha sufrido un trauma abdominal, que presenta una enfermedad sistémica subyacente que cursa con una infección agregada, que tiene compromiso vascular o hemodinámico o que consume múltiples fármacos. Los niños menores de 4 años aparentemente sanos pueden presentar pancreatitis como consecuencia de alteraciones congénitas, como el páncreas divisum, o de enfermedades metabólicas o hereditarias. Cabe destacar que estas últimas se relacionan con la pancreatitis recurrente o crónica. El diagnóstico debe confirmarse con la determinación de enzimas pancreáticas y la realización de un estudio de imagen, ya sea tomografía abdominal o resonancia magnética. El tratamiento inmediato es de sostén, manteniendo un equilibrio hidroelectrolítico y metabólico, además de evitar la estimulación pancreática (con ayuno y descompresión gástrica). En los casos graves, la evolución tiende a ser prolongada por lo que, además de estas medidas, debe instituirse un soporte nutricional oportuno a través de la nutrición parenteral o enteral vía sonda nasoyeyunal. Finalmente, es indispensable detectar y tratar oportunamente las complicaciones como: necrosis pancreática, infecciones y falla orgánica múltiple.

Suspicion of acute pancreatitis must arise with abdominal pain and oral food intolerance. This mainly occurs in a patient who has undergone abdominal trauma or presents an underlying systemic disease with an added infection, vascular or hemodynamic component, or if the patient is receiving multiple drugs. Apparently healthy children <4 years of age can display pancreatitis as a result of congenital alterations that favor the condition such as pancreas divisum and metabolic or hereditary diseases, emphasizing that the latter are related to recurrent or chronic pancreatitis. Diagnosis must be confirmed with pancreatic enzyme determination and an imaging study such as abdominal tomography or magnetic resonance. Immediate treatment is aimed at support, maintaining an appropriate hydration state and metabolic balance in addition to avoiding pancreatic stimulation through fasting and gastric decompression. In serious cases, the evolution tends to be prolonged. For this reason, in addition to these measures, opportune nutritional support must be instituted through parenteral nutrition or by enteral nutrition with nasojejunal catheter. Finally, it is indispensable to detect and to opportunely treat complications like pancreatic necrosis, secondary infection and multiple organ failure.