Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen

Introduction

Ideally, there will be reproducible markers easily and non-invasively available to test for malignancy, or alternative procedures when there is no accurate marker available. For prostate cancer, one of the most common cancers in men, levels of prostate-specific antigen (PSA) lack specificity and sensitivity for the determination of malignancy when they fall within a range of values termed the ‘grey zone’.

Objective

To examine the predictive value of sialic acid in prostate neoplasms.

Study design

In our study of diagnostic accuracy we recruited 70 men complaining of urinary symptoms who presented in the urology department as outpatients or inpatients. All patients were checked with biopsy and pathology in order to relate benign and malignant lesions of the prostate to levels of sialic acid, a member of a family of acetylated products of neuraminic acid, which has so far proved to be a very sensitive and accurate marker of malignancy.

Results

The sialic acid level was found to be elevated in patients with prostate cancer (mean 75.06 ± 10.4 mg/dl) and reduced in patients with benign prostate hyperplasia (mean 57.086 ± 8.7 mg/dl) (p < 0.01); it had a sensitivity of 86% and specificity of 84% in diagnosing malignancy.

Conclusion

Sialic acid can be used as an adjunct in predicting prostate malignancy when PSA values fall in the grey zone.     

In Vivo Acquisition of a Plasmid-Mediated blaKPC-2 Gene among Clonal Isolates of Serratia marcescens

Three patients admitted to a Greek hospital were infected with Serratia marcescens isolates that exhibited reduced susceptibility to carbapenems and harbored Klebsiella pneumoniae carbapenemase (KPC) enzymes. In two of these cases, the patients were initially infected by carbapenem-susceptible S. marcescens isolates. Molecular typing and plasmid analysis suggested that all three patients had clonally indistinguishable isolates of S. marcescens that acquired a plasmid-mediated bla_KPC-2 gene during the hospitalization.The emergence of organisms producing class A β-lactamases of Klebsiella pneumoniae carbapenemase (KPC) types is a major clinical and public health concern (2, 10). They are typically transposon-encoded determinants and therefore have the potential to disseminate between plasmids and across bacterial species (9). K. pneumoniae remains the species most likely to harbor bla_KPC genes (2, 8, 10, 13). Nevertheless, other species of Enterobacteriaceae, as well as species of nonfermenters, have been occasionally reported to exhibit this pattern of resistance (3, 15, 16, 19). In Serratia marcescens carbapenemase production is mostly attributed to class B metallo-β-lactamases (MBLs) as well as to the class A SME family of carbapenemases (14). Only recently has carbapenem-hydrolyzing activity in S. marcescens been attributed to the production of a KPC in China and the United States (3, 17, 23). We report the spread of three bla_KPC-possessing S. marcescens isolates in a Greek intensive care unit and give in vitro and in vivo evidence of the potential acquisition of such plasmid-borne resistance genes.In December 2008 a 77-year-old woman was admitted to the unit following a neurosurgical procedure. Ampicillin-sulbactam was administered postoperatively. Two months after her admission, the patient developed pneumonia, and bronchial lavage samples grew a S. marcescens isolate (S53) that exhibited reduced carbapenem susceptibility. The patient was successfully treated with tigecycline and inhaled colistin.Approximately 5 months later, in April 2009, a 49-year-old man was admitted following the surgical removal of a subcranial hematoma. He remained febrile while receiving empirical prophylactic antibiotic treatment with ampicillin-sulbactam, vancomycin, and amikacin. Bronchial lavage samples produced a carbapenem-susceptible S. marcescens isolate (S51) and a carbapenem-resistant K. pneumoniae isolate (K72). Antibiotic therapy was changed to meropenem and colistin. A second episode of pneumonia occurred approximately 2 weeks later, and a new S. marcescens isolate (S54) with reduced susceptibility to carbapenems was recovered from the bronchial lavage cultures. The patient was successfully treated with tigecycline and colistin.Finally, in April 2009 a 33-year-old woman was admitted following extensive surgery to the spine. The patient received ampicillin-sulbactam postoperatively. Approximately a week after her admission she presented with bacteremia due to a carbapenem-susceptible S. marcescens isolate (S52) and was treated with ciprofloxacin. Three weeks later the patient had an episode of pneumonia. Bronchial lavage sample cultures produced a new S. marcescens isolate (S55) that exhibited reduced susceptibility to carbapenems. Administration of ciprofloxacin in combination with gentamicin led to the successful treatment of this episode.The isolates that were recovered from the aforementioned patients were evaluated. Species identification was performed with the Vitek 2 system (bioMérieux, Marcy l''Étoile, France) and confirmed with API 20E (bioMérieux). MICs for several β-lactams, aminoglycosides, ciprofloxacin, tigecycline, and colistin were further determined by agar dilution according to CLSI recommendations (4). The MBL Etest (AB Biodisk, Solna, Sweden) and the combined disk test with imipenem and EDTA (5) were used to screen for MBL production. The phenotypic detection of KPC-possessing isolates was evaluated with the boronic acid potentiation disk test using meropenem as an antibiotic substrate (20). Extended-spectrum β-lactamase (ESBL) production was tested with the CLSI confirmatory test and in the KPC-possessing isolates with the modified CLSI ESBL confirmatory test, using clavulanate in combination with boronic acid (21).Isolates were screened for β-lactamase genes by PCR amplification using a panel of primers for the detection of all types of MBLs (6), KPCs (8), plasmid-mediated AmpCs in single PCRs for each gene (11), and ESBLs (22). PCR products were subjected to direct sequencing. Pulsed-field gel electrophoresis (PFGE) of SpeI- and of XbaI-digested genomic DNA of the S. marcescens isolates was performed with a CHEF-DRIII system (Bio-Rad, Hemel Hempstead, United Kingdom), and PFGE patterns were compared visually following previously described criteria (18). The potential for conjugational transfer of carbapenem resistance was examined in biparental matings using LB broth cultures and Escherichia coli 26R764 (lac⁺ Rif^r) as the recipient strain. Transconjugant clones were screened on MacConkey agar plates containing rifampin (150 μg/ml) and amoxicillin (40 μg/ml) or ertapenem (0.5 μg/ml). MICs were determined by agar dilution (4). All β-lactamase genes were detected by PCR amplification. Plasmid extraction was performed by using an alkaline lysis protocol with E. coli 39R861 as a control strain (7).The susceptibility patterns of the S. marcescens and K. pneumoniae isolates are shown in Table ​Table1.1. S. marcescens isolates S51 and S52 were susceptible to all carbepenems and to most β-lactam antibiotics. Phenotypic tests were negative for carbapenemase and ESBL production, amplification of the β-lactamase genes confirmed the presence solely of the bla_TEM gene, and DNA sequencing identified the gene in both isolates as bla_TEM-1.

TABLE 1.

Antimicrobial susceptibility patterns of the study''s clinical isolates, their transconjugants, and the recipient strain, E. coli 26R764

Identification of differentially expressed proteins in senescent human embryonic fibroblasts

Normal human fibroblasts undergo a limited number of divisions in culture, a process known as replicative senescence (RS). Although several senescence-specific genes have been identified, analysis at the level of protein expression can provide additional insights into the mechanisms that regulate RS. We have performed a proteomic comparison between young and replicative senescent human embryonic WI-38 fibroblasts and we have identified 13 proteins, which are differentially expressed in senescent cells. Some of the identified proteins are components of the cellular cytoskeleton, while others are implicated in key cellular functions including metabolism and energy production, Ca(2+) signalling, nucleo-cytoplasmic trafficking and telomerase activity regulation. In summary, our analysis contributes to the list of senescence-associated proteins by identifying new biomarkers and provides novel information on functional protein networks that are perturbed during replicative senescence of human fibroblast cultures.     

Late-presenting developmental dysplasia of the hip treated with the modified Hoffmann-Daimler functional method

BACKGROUND: The general consensus is that nonoperative treatment of developmental dysplasia of the hip should not be attempted for patients in whom previous treatment of the disease has failed, those in whom the disease was neglected, or those in whom the disease presented late. In such cases, it is believed that the optimum period for hip remodeling has passed and that operative methods are preferable. The purpose of the present study was to report the efficacy of a modified form of the Hoffmann-Daimler method for the treatment of late-presenting developmental dysplasia of the hip. MATERIALS: We retrospectively reviewed the records of sixty-nine patients (ninety-five hips) with neglected developmental dysplasia of the hip who had been managed nonoperatively with a modification of the Hoffmann-Daimler method from 1971 to 2000. With this method, the patient wears a flexion harness (Phase A), during which time the femoral head is gradually reduced, followed by an abduction splint (Phase B), during which time the reduced hip remodels. We have modified the original method by introducing new treatment strategies. The study group included nine boys and sixty girls. The average age of the patients was sixteen months (range, six to forty-four months) at the start of treatment and 11.5 years (range, six to twenty-nine years) at the time of the latest follow-up. Radiographs were assessed to determine the acetabular index, the Severin classification, and the presence of evidence of osteonecrosis of the proximal femoral epiphysis. Hips that were rated as Severin class I or class II were classified as satisfactory, whereas those that were rated as Severin class III or class IV were classified as unsatisfactory. RESULTS: On the basis of the most recent follow-up radiographs, eighty-eight (93%) of the dislocated hips were classified as satisfactory (sixty-seven were rated as Severin class I and twenty-one were rated as Severin class II) and seven were classified as unsatisfactory (six were rated as Severin class III and one was rated as Severin class IV). No hip was rated as Severin class V or VI. The average acetabular index was 40 degrees +/- 7.4 degrees prior to the onset of treatment and 24 degrees +/- 5.7 degrees at the end of treatment. No redislocations or other complications were noted. Osteonecrosis was noted in six of the ninety-five hips. CONCLUSIONS: Late-presenting or neglected developmental dysplasia of the hip can be successfully treated with use of a modified Hoffmann-Daimler method. The high rate of successful reduction, the low prevalence of osteonecrosis and residual dysplasia, and the limited complications may make this modified method a safe alternative to surgical treatment. LEVEL OF EVIDENCE: Therapeutic Level IV.     

Alternative access site choice after initial radial access site failure for coronary angiography and intervention

Background Transradial access for coronary catheterization is more technically challenging compared to the traditional transfemoral approach and radial access failure is quite common. The aim of this study is to describe the additional steps after initial radial access site failure in a high specialized forearm approach center. Methods A retrospective evaluation of all coronary catheterizations performed in our Department between January 2016 and December 2016 was performed, with focus on arterial access. Results One thousand three hundred forty six procedures were evaluated. The initial access site used was right radial [1173 procedures (87.1%)], left radial [120 procedures (8.9%)], right ulnar [7 procedures (0.5%)], left ulnar [40 procedures (2.9%)] and femoral approach [6 procedures (0.4%)]. Radial artery cannulation failure was observed in 37 procedures (2.9% of 1293 procedures with initial radial approach). Failure of procedure completion after successful radial sheath insertion was observed in 46 procedures (3.6%). The alternative access site after initial radial approach failure was contralateral radial [43 procedures (51.8%)], ipsilateral ulnar [22 procedures (26.5%), contralateral ulnar [12 patients (14.5%)] and femoral approach [6 procedures (7.2%)]. Conclusion Forearm arteries can be used as alternative access site after initial radial approach failure in order to reduce the use of femoral approach during cardiac catheterization.