Palivizumab prophylaxis of respiratory syncytial virus disease in 2000-2001: results from The Palivizumab Outcomes Registry

The objective of the Registry was to characterize the population of infants receiving prophylaxis for respiratory syncytial virus (RSV) disease by describing the patterns and scope of usage of palivizumab in a cross section of US infants. RSV hospitalization outcomes were also described. The Palivizumab (Synagis, MedImmune, Inc., 25 West Watkins Mill Road, Gaithersburg, MD 20878) Outcomes Registry was a prospective multicenter survey conducted at 63 sites. Demographics, injection history, and RSV hospitalization outcomes were collected on 2,116 infants receiving palivizumab. Infants were enrolled in the Registry between September 1, 2000-March 1, 2001, at the time of their first injection. Infants born at less than 32 weeks of gestation accounted for 47% of infants enrolled, and those between 32-35 weeks accounted for 45%; approximately 8% were greater than 35 weeks of gestation. Lower RSV hospitalization rates were observed in infants who had greater adherence to regularly scheduled injections. Nearly one-half of all hospitalizations occurred within the first and second injection intervals, suggesting the importance of early RSV protection. The confirmed RSV hospitalization rate of all infants in the Registry was 2.9%; the rate was 5.8% in infants with chronic lung disease of infancy, and 2.1% in premature infants without chronic lung disease. In conclusion, these data support the continued effectiveness of palivizumab prophylaxis for severe RSV lower respiratory tract disease in a large cohort of high-risk infants from geographically diverse pediatric offices and clinics. The Palivizumab Outcomes Registry provides an opportunity to assess palivizumab utilization and clinical effectiveness in the US.     

Differential expression of alpha1 (IV) and alpha5 (IV) collagen chains in basal-cell carcinoma

BACKGROUND: Basement membrane alterations are common in malignancies, and they may indicate tumoral aggressiveness. Distinct patterns of tumoral coverage by collagen IV were reported in nodular and aggressive basal-cell carcinomas (BCCs). Differential expressions of alpha (IV) collagen chains were also shown on frozen sections. The aim of our work was to document the immunohistochemical expression of alpha1, alpha3, and alpha5 (IV) collagen chains in BCC after routine fixation and processing. METHODS: The patterns of distribution of alpha1 (IV), alpha3 (IV), and alpha5 (IV) collagen chains were studied in 20 formalin-fixed and paraffin-embedded BCCs showing different infiltrative patterns. One trichoblastoma was used as control. RESULTS: In nodular BCCs, the expression of alpha5 (IV) collagen chain was downregulated and uneven. By contrast, alpha1 (IV) collagen chain expression was preserved around these tumors similar to the surrounding skin. However, the alpha1 (IV) collagen chain expression was discontinuous or absent in BCC areas showing an infiltrative pattern of extension. The alpha3 chain was absent both underneath all BCCs and non-neoplastic skin. CONCLUSIONS: The basement membrane alterations around nodular BCCs involved more precisely the alpha5 (IV) collagen chains. Defects in alpha1 (IV) collagen chain expression seemed to be associated with a tumoral invasive and infiltrative pattern. The biological significance of these findings is unclear.     

Potential role of tocilizumab in severe gastrointestinal barrier damage after CAR T-cell therapy

We report a septicemia and disseminated candidiasis due to delayed gastrointestinal mucosae repair in a patient treated with tocilizumab after anti-CD19 CAR T-cell therapy. Tocilizumab could have inhibited intestinal tissue repair and furthered bacteria translocation leading to the invasion of intestinal mucosa by yeasts as IL-6 is known to be involved in mucosal wound healing.     

FUS mutations in frontotemporal lobar degeneration with amyotrophic lateral sclerosis

Rapid advances were made in the knowledge of amyotrophic lateral sclerosis (ALS) with the recent identification of TARDBP and FUS mutations in familial ALS. More recently, FUS-positive inclusions were found in a subset of TDP-43-negative frontotemporal lobar degeneration (FTLD) prompting us to analyze FUS in FTLD and FTLD-ALS patients. The p.Arg521His mutation was identified in a patient who initially had behavioral disorders and rapidly developed ALS. Although the frequency of mutations is low, our study enlarges the phenotypes associated with FUS mutations and shows that FUS could also play a direct pathogenic role in FTLD spectrum of diseases.     

Species identification of clinical Prevotella isolates by matrix-assisted laser desorption ionization-time of flight mass spectrometry

The performance of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS) for species identification of Prevotella was evaluated and compared with 16S rRNA gene sequencing. Using a Bruker database, 62.7% of the 102 clinical isolates were identified to the species level and 73.5% to the genus level. Extension of the commercial database improved these figures to, respectively, 83.3% and 89.2%. MALDI-TOF MS identification of Prevotella is reliable but needs a more extensive database.     

Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen metabolism

Lafora disease is a fatal autosomal recessive form of progressive myoclonus epilepsy. Patients manifest myoclonus and tonic-clonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. The two genes known to be involved in Lafora disease are EPM2A and NHLRC1 (EPM2B). The EPM2A gene encodes laforin, a dual-specificity protein phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two proteins interact with each other and, as a complex, are thought to regulate glycogen synthesis. Here, we report three Lafora families with two novel pathogenic mutations (C46Y and L261P) and two recurrent mutations (P69A and D146N) in NHLRC1. Investigation of their functional consequences in cultured mammalian cells revealed that malin(C46Y), malin(P69A), malin(D146N), and malin(L261P) mutants failed to downregulate the level of R5/PTG, a regulatory subunit of protein phosphatase 1 involved in glycogen synthesis. Abnormal accumulation of intracellular glycogen was observed with all malin mutants, reminiscent of the polyglucosan inclusions (Lafora bodies) present in patients with Lafora disease.