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1.  Utility of Procalcitonin (PCT) and Mid regional pro-Adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in Emergency Department (ED). A comparison with APACHE II score 
BMC Infectious Diseases  2012;12:184.
The aim of our study was to evaluate the prognostic value of MR-proADM and PCT levels in febrile patients in the ED in comparison with a disease severity index score, the APACHE II score. We also evaluated the ability of MR-proADM and PCT to predict hospitalization.
This was an observational, multicentric study. We enrolled 128 patients referred to the ED with high fever and a suspicion of severe infection such as sepsis, lower respiratory tract infections, urinary tract infections, gastrointestinal infections, soft tissue infections, central nervous system infections, or osteomyelitis. The APACHE II score was calculated for each patient.
MR-proADM median values in controls were 0.5 nmol/l as compared with 0.85 nmol/l in patients (P < 0.0001), while PCT values in controls were 0.06 ng/ml versus 0.56 ng/ml in patients (P < 0.0001). In all patients there was a statistically significant stepwise increase in MR-proADM levels in accordance with PCT values (P < 0.0001). MR-proADM and PCT levels were significantly increased in accordance with the Apache II quartiles (P < 0.0001 and P = 0.0012 respectively).
In the respiratory infections, urinary infections, and sepsis-septic shock groups we found a correlation between the Apache II and MR-proADM respectively and MR-proADM and PCT respectively. We evaluated the ability of MR-proADM and PCT to predict hospitalization in patients admitted to our emergency departments complaining of fever. MR-proADM alone had an AUC of 0.694, while PCT alone had an AUC of 0.763. The combined use of PCT and MR-proADM instead showed an AUC of 0.79.
The present study highlights the way in which MR-proADM and PCT may be helpful to the febrile patient’s care in the ED. Our data support the prognostic role of MR-proADM and PCT in that setting, as demonstrated by the correlation with the APACHE II score. The combined use of the two biomarkers can predict a subsequent hospitalization of febrile patients. The rational use of these two molecules could lead to several advantages, such as faster diagnosis, more accurate risk stratification, and optimization of the treatment, with consequent benefit to the patient and considerably reduced costs.
PMCID: PMC3447640  PMID: 22874067
Procalcitonin; Mid regional pro-Adrenomedullin; Fever; APACHE II score
2.  Detection of Clarithromycin-Resistant Helicobacter pylori in Stool Samples 
Journal of Clinical Microbiology  2003;41(8):3636-3640.
The recognition of the role of Helicobacter pylori in gastric diseases has led to the widespread use of antibiotics in the eradication of this pathogen. The most advocated therapy, triple therapy, often includes clarithromycin. It is well known that clarithromycin resistance is one of the major causes of eradication failure. The development of a rapid noninvasive technique that could easily be performed on fecal samples and that could also provide information about the antibiotic resistance of this microorganism is therefore advisable. Previous findings have demonstrated that clarithromycin resistance is due to a single point mutation in the 23S rRNA. All the mutations described have been associated with specific restriction sites, namely BsaI (A2143G), MboII (A2142C/G), and HhaI (T2717C). On this basis we have developed a new method, a seminested PCR, allowing screening for clarithromycin resistance of H. pylori directly on stool samples. This method furnished a 783-bp fragment of the 23S rRNA, which was subsequently digested by MboII, BsaI, and HhaI, in order to identify single point mutations associated with clarithromycin resistance. Of a total of 283 stool samples examined, 125 were H. pylori positive and two of them were shown to contain clarithromycin-resistant strains due to the presence of a mutation at position 2717, whereas no PCR products contained mutations at position 2142 or 2143. In order to evaluate the reliability of the new system, we compared the results of restriction analysis of the PCR products with the MICs shown by the H. pylori isolates by culturing gastric biopsies from the same patients.
PMCID: PMC179782  PMID: 12904368
3.  New Site of Modification of 23S rRNA Associated with Clarithromycin Resistance of Helicobacter pylori Clinical Isolates 
Antimicrobial Agents and Chemotherapy  2002;46(12):3765-3769.
Resistance of Helicobacter pylori to clarithromycin occurs with a prevalence ranging from 0 to 15%. This has an important clinical impact on dual and triple therapies, in which clarithromycin seems to be the better choice to achieve H. pylori eradication. In order to evaluate the possibility of new mechanisms of clarithromycin resistance, a PCR assay that amplified a portion of 23S rRNA from H. pylori isolates was used. Gastric tissue biopsy specimens from 230 consecutive patients were cultured for H. pylori isolation. Eighty-six gastric biopsy specimens yielded H. pylori-positive results, and among these 12 isolates were clarithromycin resistant. The latter were studied to detect mutations in the 23S rRNA gene. Sequence analysis of the 1,143-bp PCR product (portion of the 23S rRNA gene) did not reveal mutation such as that described at position 2142 to 2143. On the contrary, our findings show, for seven isolates, a T-to-C transition at position 2717. This mutation conferred a low level of resistance, equivalent to the MIC for the isolates, selected using the E-test as well as using the agar dilution method: 1 μg/ml. Moreover, T2717C transition is located in a highly conserved region of the 23S RNA associated with functional sites: domain VI. This fact has a strong effect on the secondary structure of the 23S RNA and on its interaction with macrolide. Mutation at position 2717 also generated an HhaI restriction site; therefore, restriction analysis of the PCR product also permits a rapid detection of resistant isolates.
PMCID: PMC132752  PMID: 12435674

Results 1-3 (3)