Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To investigate the molecular epidemiological characteristics of the Acinetobacter baumannii strains isolated from blood and sputum samples of patients with ventilator-associated pneumonia (VAP) in ICU.Methods The patients were analyzed in two groups:Group A,A.baumannii was isolated from both blood and sputum,and Group B,A.baumannii was isolated only from sputum.Clinical data of the patients were collected,including the results of antimicrobial susceptibility test.Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were performed for the strains.Results During the study period from June 2015 to December 2105,28 nonduplicate A.baumannii strains were collected from 14 patients in group A and 28 nonduplicate strains from 28 patients in group B.The 56 A.baumannii strains were multidrug-resistant (MDR).More than 80％ of the strains were resistant to carbapenem,third-generation cephalosporins or aminoglycoside,but highly sensitive to tigecycline.No significant difference was found for the resistance rates between group A and group B.The nonduplicate A.baumannii isolates from blood and sputum samples of the same patient in group A were all homologous strains confirmed by PFGE.Six pulsotypes were identified from the 28 strains in Group A and 9 pulsotypes in Group B.Five pulsotypes were shared between the two groups.MLST analysis showed that there were 9 ST types (ST195,ST208,ST229,ST369,ST373,ST457,ST836 and two new phenotypes ST N2,ST N5) in Group A and 8 ST types (ST195,ST208,ST381 and 5 new phenotypes ST N1,ST N2,ST N3,ST N4,ST N5) strains in group B.There was no significant difference in the proportion of the main ST types between the two groups.eBURST analysis indicated that ST195,ST208,ST457,ST369,ST N1,ST N2,ST N51 belonged to CC92 prevalent strain.Conclusions The antimicrobial susceptibility profile and genotype of A.baumannii isolates from blood and sputum samples are similar.There was CC92 prevalent strain in the ward.There is no direct relation between the risk factors for bloodstream infection in VAP patients and the genotype of A.baumannii strain.It is particularly important to reinforce infection control for prevention and treatment ofA.baumannii bloodstream infections.

OBJECTIVE To investigate the distribution of acute appendicitis pathogens and their drug resistance,and to guide clinically the selection of reasonable antibiotics.METHODS Germicultures and drug sensitivity tests were conducted for the pus specimens from the 116 patients with acute appendicitis by ATB Expression bacteria(identifier).RESULTS Pathogens in 75 cases of 116 were found,with a positive rate of 64.7%,totally 85 strains of bacteria were isolated from clinical samples.Gram-negative bacilli had 72 strains,accounted for 84.7% and Gram-positives had 13 strains,(accounted) for 15.3%.The first three were Escherichia coli(54.1%),Pseudomonas aeruginosa(4.7%),and Klebsiella pneumoniae(4.7%).Sensitivity tests showed that resistance rates of E.coli to cefapirin,imipenem,compound(piperacillin),cefoxitin,and amikacin were 0,2.2%,10.9%,17.4%, and(23.9%).CONCLUSIONS Dominant pathogens in patients with acute(appendicitis) are intestinal bacilli,with(predominance) of E.coli;more emphasis should be placed on pathogen detections and drug sensitivity tests so that effective antibiotics could be selected and resistant bacteria be reduced and nosocomial infections be prevented.