Many of the leukocyte CPD have been identified as useful parameters of sepsis. Hopefully, these parameters can ultimately be incorporated into a decision rule for the screening of sepsis samples and to discriminate fungemia from bacteremia.

Hypermucoviscous (HV) isolates of Klebsiella pneumoniae have been linked to virulence potential in experimental infections. We examined 33 isolates of K. pneumoniae from patients with bacteraemia for the HV phenotype on agar culture, and determined their virulence potential by screening for capsular (K) serotype by polymerase chain reaction and the presence of seven virulence factor genes. Fourteen (42·4%) isolates expressed the HV phenotype and 11 of these were serotype K1 or K2; these serotypes were not identified in HV-negative isolates. The genes rmpA, rmpA2, aerobactin, wabG and allS were significantly more frequent in HV than non-HV isolates. Multilocus sequence typing identified 21 sequence types (ST), eight of which were found in HV-positive isolates and the clonal relatedness of isolates of the most frequent types (ST23 and ST11) from different hospitals was confirmed by pulsed-field gel electrophoresis. The HV phenotype was more associated with community-acquired infection with a lower frequency of fatal underlying illness, but with significantly more focal infections, notably liver abscesses. Clinicians should be aware of such clinical impacts of the HV phenotype.

Background To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). Methods We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. Results A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. Conclusions Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

BackgroundWe reviewed patients with multiple myeloma (MM) in order to assess the incidence of genetic abnormalities and their associations with clinical parameters, risk groups, and prognosis.MethodsA total of 130 patients with MM were enrolled. The incidences of genetic abnormalities were determined in all patients. The relationships of the genetic abnormalities and clinical parameters were investigated. In addition, a survival analysis was performed.ResultsAbnormal karyotypes were detected in 42.3% (N=55) of the patients, and this was increased to 63.1% (N=82) after including the results determined with interphase FISH. Hypodiploidy was observed in 7.7% (N=10) of the patients, and all were included in the group with complex karyotypes (30.8%, N=40). The 14q32 rearrangements were detected in 29.2% (N=38) of the patients, and these most commonly included t(11;14), which was followed by t(4;14) and t(14;16) (16.2%, 11.5%, and 0.8%, respectively). Abnormal karyotypes and complex karyotypes were associated with disease progression markers, including low hemoglobin levels, low platelet counts, high plasma cell burden, high β2-microglobulin, and high international staging system stages. A high free light chain (FLC) ratio and FLC difference were associated with abnormal karyotypes, complex karyotypes, and higher plasma cell burden. Hypodiploidy and low platelet counts were significant independent prognostic factors and were more important in patient outcome than any single abnormality.ConclusionsGenetic abnormalities were associated with disease progression markers and prognosis of MM patients.

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We identified principal genetic alterations in 97.1% (99/102) of patients with T-acute lymphoblastic leukemia (T-ALL) using integrative genetic analyses, including massive parallel sequencing and multiplex ligation-dependent probe amplification (MLPA). A total of 133 mutations were identified in the following genes in descending order: NOTCH1 (66.7%), FBXW7 (19.6%), PHF6 (15.7%), RUNX1 (12.7%), NRAS (10.8%), and DNMT3A (9.8%). Copy number alterations were most frequently detected in CDKN2B, CDKN2A, and genes on 9p21.3 in T-ALL (45.1%). Gene expression data demonstrated the downregulation of CDKN2B in most cases of T-ALL, whereas CDKN2A downregulation was mainly restricted to deletions. Additional quantitative methylation analysis demonstrated that CDKN2B downregulation stemmed from deletion and hypermethylation. Analysis of 64 patients with CDKN2B hypermethylation indicated an association with an older age of onset and early T cell precursor ALL, which involved very early arrest of T cell differentiation. Genes associated with methylation and myeloid neoplasms, including DNMT3A and NRAS, were more commonly mutated in T-ALL with CDKN2B hypermethylation. In particular, a CDKN2B biallelic deletion or high methylation level (≥45%), the age of onset, and the GATA3 and SH2B3 mutations were factors associated with a poor prognosis. This study clarifies that one of the most important genetic events in T-ALL, namely, CDKN2B downregulation, occurs mechanistically via deletion and hypermethylation. Different susceptible genetic backgrounds exist based on the CDKN2B downregulation mechanism.

SET-NUP214 rearrangement is a recently recognized recurrent chromosomal translocation mostly observed in T-ALL. In order to characterize this rare entity, we performed phenotypic and genetic characterization of SET-NUP214 rearrangement through an investigation of a series of 40 consecutive samples of adult T-ALL that was selected among 229 adult ALL cases during 4 years in a single institution. Four cases (10%) of SET-NUP214 translocation were identified in our study. In all cases, diagnosis of T-ALL was established according to the World Health Organization (WHO) classification, and clonal TCR rearrangements were found. The immunophenotypic markers were indicative of the precursor nature of T lymphoblasts, and they expressed one or both of the myeloid-associated antigens (CD13, CD33). Conventional cytogenetic analysis revealed complex chromosomal aberrations in all four SET-NUP214 rearranged cases and del(12)(p13)/ETV6 was frequently involved. Array-CGH demonstrated additional genomic imbalances in addition to deletion 9q34. The genomic breakpoint sequencing identified breakpoints at SET intron 7 and NUP214 intron 17, and random nucleotide addition was found in two cases at the site of rearrangement. Our independently derived data set from a single institution confirms previous findings of SET-NUP214 rearrangement, indicates the relatively high incidence of SET-NUP214 rearrangement in adult T-ALLs, and also demonstrates comprehensive clinical, phenotypic, and genetic characteristics of this entity. Also, our report on genomic breakpoints demonstrates the homogeneity in the localization of the genomic breakpoints at 9q34. Concurrent chromosomal aberrations identified in this study should provide further areas of interest in investigation of SET-NUP214-mediated leukemogenesis.

The novel method is an easily applicable and efficient measure that allows dissociation of platelet clumps, based on the pathophysiological mechanism of EDTA-PTCP.