Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome.

Sézary syndrome (SS) is a leukemic variant of cutaneous T-cell lymphoma (CTCL) and represents an ideal model for study of T-cell transformation. We describe whole-exome and single-nucleotide polymorphism array-based copy number analyses of CD4(+) tumor cells from untreated patients at diagnosis and targeted resequencing of 101 SS cases. A total of 824 somatic nonsynonymous gene variants were identified including indels, stop-gain/loss, splice variants, and recurrent gene variants indicative of considerable molecular heterogeneity. Driver genes identified using MutSigCV include POT1, which has not been previously reported in CTCL; and TP53 and DNMT3A, which were also identified consistent with previous reports. Mutations in PLCG1 were detected in 11% of tumors including novel variants not previously described in SS. This study is also the first to show BRCA2 defects in a significant proportion (14%) of SS tumors. Aberrations in PRKCQ were found to occur in 20% of tumors highlighting selection for activation of T-cell receptor/NF-κB signaling. A complex but consistent pattern of copy number variants (CNVs) was detected and many CNVs involved genes identified as putative drivers. Frequent defects involving the POT1 and ATM genes responsible for telomere maintenance were detected and may contribute to genomic instability in SS. Genomic aberrations identified were enriched for genes implicated in cell survival and fate, specifically PDGFR, ERK, JAK STAT, MAPK, and TCR/NF-κB signaling; epigenetic regulation (DNMT3A, ASLX3, TET1-3); and homologous recombination (RAD51C, BRCA2, POLD1). This study now provides the basis for a detailed functional analysis of malignant transformation of mature T cells and improved patient stratification and treatment.

Blood spatter in oral surgery: Prevalence and risk factors.

BACKGROUND: Oral surgeons are exposed to blood spatter. The authors evaluated the prevalence of and risk factors for blood spatter in facial masks during oral surgery procedures. METHODS: The authors evaluated facial masks and caps of oral surgeons and assistants for blood spatter using the Kastle-Meyer test after different oral surgery procedures. The authors correlated the presence of blood spatter to the clinician, type of surgery, surgery time, and self-awareness of blood spatter, using χ2 and t tests. RESULTS: The authors analyzed a total of 202 samples and detected blood particles in 46% of the samples in both operators and assistants. The authors observed blood contamination in all types of procedures, and in 4% of the cases, the internal part of the visor was also affected. Clinicians were unaware of the presence of blood spatter in 40% of the cases. CONCLUSIONS: The risk of clinician contamination with blood during tooth extraction and implant placement was 46%. The risk increased with the use of high-speed instruments and longer surgery time. PRACTICAL IMPLICATIONS: The use of facial protective devices should be mandatory during oral surgery procedures to avoid blood contamination, especially when rotary devices are used. In many cases, imperceptible blood spatter is present.

[Epidemiological analysis of tuberculous lymphadenopathy in a District of Barcelona: proposal of a diagnostic algorithm]. / Valoración epidemiológica de la linfadenitis tuberculosa en un distrito de Barcelona: propuesta de algoritmo diagnóstico.

BACKGROUND: Barcelona (Spain) has experienced a dramatic change in its demography, which is reflected in the local epidemics of tuberculous lymphadenopathy (TL). The objective of the study is to analyze the associated risk factors to TL in a district of Barcelona with an incidence above 50 cases per 10,000 inhabitants/year, which will help to construct a diagnostic algorithm. METHODS: single-centre retrospective cohort study of all cases of TL diagnosed between 1990 and 2009. Due to the demographic changes, we analyzed 2 separate study periods (1990-1999 and 2000-2009). Socio-demographic, clinical and diagnostic features were assessed and compared between both cohorts and the algorithm was constructed with these results. Data was obtained from all the patients diagnosed with TL in Hospital del Mar (Barcelona) and was sent to the Public Health Agency of Barcelona. RESULTS: in the first study period, 152 patients had TL (73.7% Spanish-born) and in the second study period 147 (70.7% immigrants). In the first period, the percentage of male immigrants was 70.5% and 57.1% were younger than 35 years old but in the second study period, there was a 58.1% of Spanish-born female patients and 69.8% above 35 years old. The percentage of HIV co-infection decreased from 69.9% to 44.2% in the second period but use of immunosuppressive treatment increased to 9.3% in Spanish-born patients. Multivariate analysis showed intravenous drug use (OR 8.2; 95%CI: 3.4-19.8) and immigrant status (OR 4.8; 95%CI: 2.7-8.3) as risk factors associated to TL. CONCLUSION: male immigrants arriving from areas with high burden of TB, younger than 35 years old and Spanish-born women, older than 35 years old, with HIV infection (although with a lower proportion than before year 2000) or receiving immunosuppressive treatment, are the groups with an increased risk of TL in our district.

Community-onset healthcare-related urinary tract infections: comparison with community and hospital-acquired urinary tract infections.

OBJECTIVES: To analyze the characteristics of infection, adequacy of empirical treatment and outcome of patients with community-onset healthcare-associated (HCA) urinary tract infections (UTI) and compare them with hospital (HA) and community-acquired (CA) UTI. METHODS: Prospective observational cohort study performed at a university 600-bed hospital between July 2009 and February 2010. Patients with UTI requiring hospital admission were included. Epidemiological, clinical and outcome data were recorded. RESULTS: 251 patients were included. Patients with community-onset HCA UTI were older, had more co-morbidities and had received previous antimicrobial treatment more frequently than CA UTI (p = 0.02, p = 0.01 and p < 0.01). ESBL-Escherichia coli and Pseudomonas aeruginosa infections were more frequent in HCA than in CA UTI (p = 0.03 and p < 0.01). Inadequate empirical treatment was not significantly different between community-onset HCA and CA. Factors related to mortality were P. aeruginosa infection (OR 6.51; 95%CI: 1.01-41.73), diabetes mellitus (OR 22.66; 95%CI: 3.61-142.21), solid neoplasia (OR 22.48; 95%CI: 3.38-149.49) and age (OR 1.15; 95%CI 1.03-1.28). CONCLUSIONS: Epidemiological, clinical and microbiological features suggest that community-onset HCA UTI is different from CA and similar to HA UTI. However, in our series inadequate empirical antimicrobial therapy and mortality were not significantly higher in community-onset HCA than in CA UTI.