Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a ‘borderline’ (BL) percentage of mutations (i.e. 97–97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL-CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M-CLL (n = 338) and significantly longer than that of UM-CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL-CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL-CLL remained comparable to that of M-CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL-CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL-CLL: n = 47, 4·3%). BL-CLL at diagnosis showed a biological profile comparable to that of M-CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL-CLL is good and similar to that of M-CLL, with the exception of subset #2 cases.     

Epidemic Diffusion of OXA-23-Producing Acinetobacter baumannii Isolates in Italy: Results of the First Cross-Sectional Countrywide Survey

Carbapenem-resistant Acinetobacter baumannii (CRAb) is emerging worldwide as a public health problem in various settings. The aim of this study was to investigate the prevalence of CRAb isolates in Italy and to characterize their resistance mechanisms and genetic relatedness. A countrywide cross-sectional survey was carried out at 25 centers in mid-2011. CRAb isolates were reported from all participating centers, with overall proportions of 45.7% and 22.2% among consecutive nonreplicate clinical isolates of A. baumannii from inpatients (n = 508) and outpatients (n = 63), respectively. Most of them were resistant to multiple antibiotics, whereas all remained susceptible to colistin, with MIC₅₀ and MIC₉₀ values of ≤0.5 mg/liter. The genes coding for carbapenemase production were identified by PCR and sequencing. OXA-23 enzymes (found in all centers) were by far the most common carbapenemases (81.7%), followed by OXA-58 oxacillinases (4.5%), which were found in 7 of the 25 centers. In 6 cases, CRAb isolates carried both bla_OXA-23-like and bla_OXA-58-like genes. A repetitive extragenic palindromic (REP)-PCR technique, multiplex PCRs for group identification, and multilocus sequence typing (MLST) were used to determine the genetic relationships among representative isolates (n = 55). Two different clonal lineages were identified, including a dominant clone of sequence type 2 (ST2) related to the international clone II (sequence group 1 [SG1], SG4, and SG5) and a clone of ST78 (SG6) previously described in Italy. Overall, our results demonstrate that OXA-23 enzymes have become the most prevalent carbapenemases and are now endemic in Italy. In addition, molecular typing profiles showed the presence of international and national clonal lineages in Italy.     

Successful closure of a coronary vessel rupture with a vein graft stent: Case report

We report a successful percutaneous closure of a brisk coronary artery rupture with a custom-made “vein graft stent,” a Palmaz-Schatz stent covered with a vein graft. This method is an elegant and effective alternative to the traditional surgical approach and should be considered whenever technically and clinically feasible. © 1996 Wiley-Liss, Inc.     

X-linked mental retardation with thin habitus,osteoporosis, and kyphoscoliosis: Linkage to Xp21.3-p22.12

We reevaluated a family previously described as having nonspecific X-linked mental retardation (XLMR) by Snyder and Robinson [1969: Clin Pediatr 8:669–674] (MIM 309583). Clinical and DNA studies were conducted on 17 relatives, including 6 males with mild-to-moderate mental retardation, 3 carrier females, and 8 normal males. In contrast to the normal appearance and minimal clinical findings reported 22 years ago, affected males were found to have a characteristic set of clinical findings. These developed gradually over the first 2 decades, and included thin body build with diminished muscle mass, osteoporosis and kyphoscoliosis, slight facial asymmetry with a prominent lower lip, nasal speech, high narrow or cleft palate, and long great toes. Carrier females were clinically normal. Multipoint linkage analysis indicated linkage to markers distal to the 3′ end of DMD (DXS41 and DXS989), with a maximal lod score of 4.7. On the basis of these findings, this entity is redefined as XLMR syndrome. © 1996 Wiley-Liss, Inc.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Interobserver agreement among endoscopists on evaluation of polypoid colorectal lesions visualized with the Pentax i-Scan technique

Background and aimsAdvances in colonoscopy, such as the Pentax i-Scan electronic technique, have the potential to improve the early detection of colorectal cancer. The aim of this multicentre study was to assess the interobserver agreement in the visualization of the surface and margins of colorectal polyps and in distinguishing neoplastic from non-neoplastic polyps.Patients and methodsEight expert endoscopists examined 400 mixed previously recorded images of polyps taken with different Pentax i-Scan settings in order to give an evaluation of the surface of the polyp and regular colonic mucosa, the pit-pattern and the nature of the lesion.ResultsA total of 400 mixed images of polyps with a diameter >5 mm and <10 mm were stored for analysis. Overall, there was a K_f agreement of 0.370 (p < 0.001) and 0.306 (p < 0.001) regarding pit-pattern and margins, respectively. The K_f agreement for the difference between neoplastic and non-neoplastic lesions was of 0.446 (p < 0.001).ConclusionsWe observed good interobserver agreement in the evaluation of neoplastic and non-neoplastic lesions and poor agreement in the evaluation of pit-pattern and margins. Adequate training is required in order to interpret images acquired with the i-Scan technique.     

A meta-analysis of the prognostic significance of cardiopulmonary exercise testing in patients with heart failure

The objective of the study is to assess the role of cardiopulmonary exercise testing (CPX) variables, including peak oxygen consumption (VO₂), which is the most recognized CPX variable, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, the oxygen uptake efficiency slope (OUES), and exercise oscillatory ventilation (EOV) in a current meta-analysis investigating the prognostic value of a broader list of CPX-derived variables for major adverse cardiovascular events in patients with HF. A search for relevant CPX articles was performed using standard meta-analysis methods. Of the initial 890 articles found, 30 met our inclusion criteria and were included in the final analysis. The total subject populations included were as follows: peak VO₂ (7,319), VE/VCO₂ slope (5,044), EOV (1,617), and OUES (584). Peak VO₂, the VE/VCO₂ slope and EOV were all highly significant prognostic markers (diagnostic odds ratios ≥ 4.10). The OUES also demonstrated promise as a prognostic marker (diagnostic odds ratio = 8.08) but only in a limited number of studies (n = 2). No other independent variables (including age, ejection fraction, and beta-blockade) had a significant effect on the meta-analysis results for peak VO₂ and the VE/VCO₂ slope. CPX is an important component in the prognostic assessment of patients with HF. The results of this meta-analysis strongly confirm this and support a multivariate approach to the application of CPX in this patient population.