A false positive case of high-sensitivity cardiac troponin in a patient with acute chest pain: Analytical study of the interference.

We report a case of a heterophile antibodies interference in a new high-sensitivity troponin commercial immunoassay (cTNIH Siemens), observed in a patient with possible acute coronary syndrome (ACS). The analytical interference was investigated with standard laboratories procedures. The false positive result was found with different troponin methods and kits. We also investigated the protein sequence of cTnl and no sequence variants were detected. The discordance between clinical pictures and high concentration of cTnl, together with the collaboration between clinicians and laboratory staff avoided possible erroneous diagnosis and further invasive investigations to the patient.

Amiodarone or lidocaine for cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Guidelines for treatment of out-of-hospital cardiac arrest (OOH-CA) with shockable rhythm recommend amiodarone, while lidocaine may be used if amiodarone is not available. Recent underpowered evidence suggests that amiodarone, lidocaine or placebo are equivalent with respect to survival at hospital discharge, but amiodarone and lidocaine showed higher hospital admission rates. We undertook a systematic review and meta-analysis to assess efficacy of amiodarone vs lidocaine vs placebo. METHODS: We included studies published in PubMed and EMBASE databases from inception until May 15th, 2016. The primary outcomes were survival at hospital admission and discharge in OOH-CA patients enrolled in randomized clinical trials (RCT) according to resuscitation with amiodarone vs lidocaine vs placebo. If feasible, secondary analysis was performed including in the analysis also patients with in-hospital CA and data from non-RCT. RESULTS: A total of seven findings were included in the metanalysis (three RCTs, 4 non-RCTs). Amiodarone was as beneficial as lidocaine for survival at hospital admission (primary analysis odds ratio-OR 0.86-1.23, p=0.40) and discharge (primary analysis OR 0.87-1.30, p=0.56; secondary analysis OR 0.86-1.27, p=0.67). As compared with placebo, survival at hospital admission was higher both for amiodarone (primary analysis OR 1.12-1.54, p<0.0001; secondary analysis OR 1.07-1.45, p<0.005) and lidocaine (secondary analysis only OR 1.14-1.58, p=0.0005). With regards to hospital discharge there were no differences between placebo and amiodarone (primary outcome OR 0.98-1.44, p=0.08; secondary outcome OR 0.92-1.33, p=0.28) or lidocaine (secondary outcome only OR 0.97-1.45, p=0.10). CONCLUSIONS: Amiodarone and lidocaine equally improve survival at hospital admission as compared with placebo. However, neither amiodarone nor lidocaine improve long-term outcome.

Association of IL-8 and eNOS polymorphisms with clinical outcomes in bevacizumab-treated breast cancer patients: an exploratory analysis

Background. The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. Patients and methods. eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. Results. Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. Conclusion. These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials (AU)

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Association of IL-8 and eNOS polymorphisms with clinical outcomes in bevacizumab-treated breast cancer patients: an exploratory analysis.

BACKGROUND: The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. PATIENTS AND METHODS: eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. RESULTS: Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. CONCLUSION: These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.

Use of beta-blockers in non-cardiac surgery: an open debate.

The perioperative use of beta-blockers (BBs) with the aim of decreasing perioperative adverse cardiac events has been strongly supported, especially after the publication of two small trial (McSPI and DECREASE I) that showed major benefits. However, some later trials did not confirm these benefits. The POISE trial, with 8351 patients, showed reduced primary outcomes (cardiac death, non-fatal myocardial infarction, non-fatal cardiac arrest) at the expense of significant harm, increasing all-cause and sepsis-related deaths, and doubling the incidence of stroke. These results led to revised American and European guidelines. The American guideline recommended a substantial narrowing of indication for perioperative BBs, while the European guideline remained far more liberal. Since the publication of the results of POISE, meta-analyses and new studies have been published. In this review the most recent available evidence, the changes in the guidelines and the criticism on POISE results are discussed together with reasons why recent meta-analyses may not have greater certainty. This is explained by the huge numeric influence of the POISE trial and the heterogeneity in the design of the trials on perioperative BBs. Thus all the evidence available must now be taken into consideration to develop more appropriate guidelines to minimise the risks and enhance the benefits of perioperative beta-blockade.

Liver function test abnormalities after traumatic brain injury: is hepato-biliary ultrasound a sensitive diagnostic tool?

BACKGROUND: This study was to evaluate the usefulness of hepato-biliary ultrasound (HBUS) for the investigation of isolated liver function tests (LFTs) abnormalities. METHODS: We retrospectively reviewed HBUS reports in traumatic brain injury (TBI) patients admitted to our tertiary neuro-critical care unit (NCCU; January 2005-June 2011). We included patients receiving an HBUS for isolated LFTs derangement, excluding pre-existing hepato-biliary diseases or trauma. We assessed the temporal profile of alanine aminotransferase (ALT), bilirubin (Bil), and alkaline phosphatase (ALP). RESULTS: Of 511 patients, 58 received an HBUS. Of these, 47 were investigated for isolated LFTs derangement; HBUS always failed to identify a cause for these abnormalities. The HBUS was performed on day 18 (range 6-51) with the following mean values: 246 IU litre(-1) [ALT, 95% confidence interval (CI) 183-308], 24 µmol litre(-1) (Bil, 95% CI 8-40), and 329 IU litre(-1) (ALP, 95% CI 267-390); only ALT (72, 95% CI 36-107) and ALP (73, 95% CI 65-81) were deranged from admission values (both P<0.01). At NCCU discharge, both ALT (160, 95% CI 118-202) and ALP (300, 95% CI 240-360) were higher than at admission (P<0.01). Compared with HBUS-day value, only ALT improved by NCCU discharge (P<0.05), while both were recovering by hospital discharge (ALT 83, 95% CI 59-107; ALP 216, 95% CI 181-251; P<0.01). At hospital discharge, ALP remained higher than at admission (P<0.01). CONCLUSIONS: In TBI patients, HBUS did not appear sensitive in detecting causes for isolated LFT abnormalities. Both ALT and ALP worsened and gradually recovered. Their abnormalities did not prevent NCCU discharge. ALP recovered more slowly than ALT. TBI and its complications, critical illness, and pharmacological strategies may explain the LFTs derangement.

End-of-life care is still a challenge for Italy.

The aim of this paper was to review current end of life (EOL) practice in Italy. The authors have made an appraisal of the existing literature in order to understand current end of life care practice in Italy. This manuscript focuses on analyzing the dying process, the transoceanic similarities and differences in the end of life decision-making practice, and the family involvement. The authors acknowledge the importance of the recent Englaro court case verdict on current practice in Italy. Dying has changed as a process over the last century in term of causes of death, costs, communication of the prognosis, and needs of the patient's family. Regardless of national and international guidelines, there is no agreement among Italian doctors regarding the gold standards of daily clinical practice at the EOL.

Association between cutaneous melanoma, Breslow thickness and vitamin D receptor BsmI polymorphism.

BACKGROUND: Literature data report an association between some vitamin D receptor (VDR) polymorphisms and different kinds of tumours, including malignant melanoma (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been investigated in association with the presence of cutaneous MM or the development of metastases. OBJECTIVES: The present paper analyses for the first time the association between BsmI polymorphism and MM prevalence together with Breslow thickness. In addition, the FokI single nucleotide polymorphism was also determined. METHODS: One hundred and one patients with MM and 101 healthy donors matched for age and sex were enrolled. Molecular VDR typing was performed by means of restriction fragment length polymorphism analysis. RESULTS: All cases and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G. Significant associations were found between the BsmI bb genotype frequency and MM (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression analysis confirmed these significant results after correction for age, gender, skin type and MM localization. CONCLUSIONS: Although the biological meaning of the effects exerted by BsmI polymorphism is still under debate, the statistical association found in the present study suggests that further work should be done to verify this variant as a possible risk marker for MM and its aggressiveness, also considering that the real association may be due to other unknown genes linked to the BsmI b allele.

Slight association between type 1 diabetes and "ff" VDR FokI genotype in patients from the Italian Lazio Region. Lack of association with diabetes complications.

BACKGROUND: Vitamin D receptor (VDR) mediates the effects of vitamin D. Our paper evaluates the FokI and BsmI VDR genotypes in 246 Caucasian (Italian from Lazio Region) T1DM patients compared with 246 Caucasian healthy controls, sharing age and gender and regional provenience with the patients. In addition, T1DM patients without complications were compared with those carrying three complications. METHODS: Genotyping has been obtained by RFLP-PCR technique. RESULTS: A slight significant association of T1DM with FokI homozygous "f" genotype was observed. No association was observed with the presence of multiple complications by a multivariate analysis. CONCLUSION: T1DM patients showed slightly increased prevalence of "ff" VDR genotype.

First genetic analysis of lattice corneal dystrophy type I in a family from Bulgaria.

PURPOSE: To report a new family belonging to a previously non-investigated geographic are a with a rare form of lattice corneal dystrophy (LCD). METHODS: Detailed ophthalmologic analysis was carried out on a Bulgarian woman, enrolled for perforating keratoplasty. In order to obtain a final diagnosis both histology and genetic analysis were performed. RESULTS: Upon transplantation, histologic analysis of the dystrophic cornea revealed the typical staining pattern and amyloid deposits of lattice corneal dystrophies. Genetic analysis of the subject and her daughter confirmed the presence of an autosomal dominant R124C mutation within exon 4 of the BIGH3 gene, encoding for keratoepithelin, while showing no abnormalities in her son. CONCLUSIONS: The identification of this mutation allows the unambiguous classification of this corneal dystrophy as LCD type I. A first case of LCD I in a family from Eastern Europe could help to better clarify the molecular epidemiology of the disease.