Malaria in pediatric age in the Piedmont Region

Introduction. Pediatric malaria, even in countries considered as free as Italy, is an important problem of public health because children have a high variability of the clinical picture. The objective of this brief note is to determine the incidence of pediatric malaria in the Piedmont Region during the period 1989-2015.Materials and methods. All cases of pediatric malaria notified were considered thanks to the regional information flow over the period 1989-2015. Cases of congenital malaria, unconfirmed malaria cases, and aged 14 and older were excluded of the study.Results. In Piedmont in the period 1989-2015, pediatric malaria accounts for 8.8% of the total (172/1946 cases). 74% of patients are of foreign nationality, to which must be added the 14% represented by those born in Italy from foreign parents, while it is 100% the fraction of patients who have made a trip to the abroad. The notification of cases is greater in the autumn months. Only 7.6% of the sample carried out a complete chemoprophylaxis. In 79% of cases, the primary care physician advised chemoprophylaxis on trips to endemic areas.Conclusions. At present, lacking an effective vaccine, the prevention and implementation of standard precautions such as chemoprophylaxis, represent the safest strategy to put into practice to eradicate the disease especially for the groups at greater risk as visiting friends and relatives

Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC)

Prognostic impact of a 3-MicroRNA signature in cytological samples of small cell lung cancer

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive neoplasm that accounts for approximately 10% to 15% of lung cancers. In most cases, the diagnosis relies on cytology and needs to be confirmed by immunohistochemistry. Although several genetic and molecular abnormalities have been recorded, molecular markers able to predict the prognosis are still lacking. MicroRNA (miRNA) signatures have been recently proposed as useful biomarkers in lung cancer because of their high stability during standard sample processing. METHODS: Cytological samples for 50 patients with SCLC were collected from primary tumors (n = 25) and metastases (n = 25) by means of fine-needle aspiration (FNA) or bronchial washing (BW); they were fixed in ethanol (FNA) or Duboscq-Brazil fluid (BW). The 3-miRNA panel expression (miR-192, miR-200c, and miR-205) was quantified with a TaqMan polymerase chain reaction miRNA assay and was compared with overall survival (OS) and clinicopathological data. RESULTS: All samples had sufficient RNA for the miRNA expression analysis to be performed, regardless of the sample source or the fixative medium. Patients with a low expression level of the 3-miRNA panel were associated with better OS in univariate (P = .032) and multivariate analyses (P = .022). Moreover, in the group of patients older than the mean age of our cohort (65.8 years), a significant OS advantage (P = .013) was seen for patients with a low expression level of the 3-miRNA panel. CONCLUSIONS: A specific 3-miRNA signature is potentially useful for predicting survival for patients with SCLC, and it may be feasible with cytological samples taken during standard diagnostic procedures

A multistep cytological approach for patients with jaundice and biliary strictures of indeterminate origin

AIMS. Fluorescence in situ hybridisation (FISH) increases the sensitivity for detecting pancreatobiliary tract cancer over routine cytology. In this study, diagnostic accuracy and costs of cytology and FISH in detecting cancer in patients with jaundice with biliary strictures were assessed. METHODS. Brushing specimens from 109 patients with jaundice were obtained during endoscopic retrograde cholangiopancreatography and examined by cytology and FISH. The specimens were considered FISH-positive for malignancy if at least five polysomic cells or 10 cells with homozygous or heterozygous 9p21/p16 deletion were detected. Definitive diagnosis of the stricture as benign or malignant relied on surgical pathology (45 cases) or clinical-radiological follow-up >18\u2005months (64 cases). We calculated costs of cytology and FISH based on the reimbursement from the Piedmont region, Italy (respectively, \u20ac33 and \u20ac750). RESULTS. Ninety of 109 patients had evidence of malignancy (44 pancreatic carcinomas, 36 cholangiocarcinomas, 5 gallbladder carcinomas, 5 other cancers), while 19 had benign strictures. Routine cytology showed 42% sensitivity, but 100% specificity for the diagnosis of malignancy, while FISH-polysomy showed 70% sensitivity with 100% specificity and FISH-polysomy plus homozygous or heterozygous 9p21/p16 deletion showed 76% sensitivity with 100% specificity. The cost per additional correct diagnosis of cancer obtained by FISH, in comparison with cytology, was \u20ac1775 using a sequential cytological approach (ie, performing FISH only in patients with negative or indeterminate cytology). CONCLUSIONS. FISH should be recommended as the second step in detecting cancer in patients with jaundice with pancreatobiliary tract strictures and cytology negative or indeterminate for malignancy

KRAS mutation testing on all non-malignant diagnosis of pancreatic endoscopic ultrasound-guided fine-needle aspiration biopsies improves diagnostic accuracy

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the procedure of choice for the cytologic diagnosis of pancreatic masses. The specificity of EUS-FNA approaches 100%, but the sensitivity is still low, and the high rate of indeterminate (atypical and suspicious) and false-negative results needs improvement. KRAS gene is frequently mutated in pancreatic ductal adenocarcinoma (PDAC) (up to 90%), and mutation analysis of KRAS has been proposed as diagnostic biomarker of PDAC. In most laboratories, KRAS mutation testing is performed by Sanger sequencing or real time-quantitative polymerase chain reaction (RT-qPCR), but these methods may give false-negative results in routine samples, mainly due to low cellularity. In order to increase the sensitivity of EUS-FNA, we propose a sequential approach for detecting KRAS mutations using mutant enriched-PCR (ME-PCR, sensitivity up to 0.1%) in cytologically indeterminate and negative samples tested wild-type by RT-qPCR. EUS-FNA specimens from 107 patients with pancreatic masses (51 males, 56 females, mean age 67 years) were cytologically examined. According to the Papanicolaou Society of Cytopathology guidelines, 50 cases (47%) were classified malignant, 15 (14%) suspicious, 13 (12%) atypical and 10 (9%) negative for malignancy; 18 cases (17%) were non-diagnostic. The overall specificity and sensitivity of cytological examination were 100% and 61%, respectively, when only negative and positive cases were considered; when atypical and suspicious were added to positive cases, the sensitivity increased to 95.1% and the specificity decreased to 85.7%. In all the cases, DNA was extracted from the cell-block and KRAS mutations were investigated by RT-qPCR, followed by ME-PCR in non-amplifiable and negative cases. The overall sensitivity and specificity of KRAS mutation testing alone were 79.3% and 100%; when KRAS mutation testing was performed in indeterminate and negative cytology, the sensitivity increased to 90% with specificity to 100%. Our data indicate that conventional cytology from EUS-FNA samples is highly specific for the diagnosis of pancreatic cancer. Indeterminate and negative cases need to be screened for KRAS mutations; this two-step approach may greatly improve the diagnostic accuracy of this method

Heterozygous β‐globin gene mutations as a risk factor for iron accumulation and liver fibrosis in chronic hepatitis C

BACKGROUND: Iron accumulation is a well-known risk factor for the progression of chronic hepatitis C (CHC) to fibrosis. However, the profibrogenic role of the genes controlling iron homeostasis is still controversial. AIM: To evaluate the relative role of haemachromatosis (HFE), ferroportin and beta-globin gene mutations in promoting iron accumulation and fibrosis in patients with CHC. METHODS: Genetic analysis was performed together with the assessment of hepatic iron content and histology in 100 consecutive HIV-antibody and hepatitis B surface antigen-negative patients with biopsy-proven CHC. RESULTS: Among the patients investigated, 12 were heterozygous for various beta-globin gene mutations (39[C-->T], IVS1.1[G-->A], 22 7 bp deletion and IVS1.6[T-->C]) and 29 carried HFE (C282Y, H63D and S65C) gene mutations. One further patient was heterozygous for both HFE (H63D) and beta-globin (39[C-->T]) variants, whereas 58 had the wild-type alleles of both the genes. Hepatic iron concentration (HIC) and hepatic stainable iron were significantly higher (p2) was observed in 48 of 100 patients. Logistic regression demonstrated that age (OR 1.05; 95% CI 1.02 to 1.09; p<0.005) and beta-globin mutations (OR 4.99; 95% CI 1.22 to 20.3; p = 0.025) were independent predictors of the severity of fibrosis. CONCLUSIONS: Heterozygosis for beta-globin mutations is a novel risk factor for both hepatic iron accumulation and the progression to fibrosis in patients with CHC

Gene-asbestos interaction in malignant pleural mesothelioma susceptibility

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, on average less than 10% of subjects highly exposed to asbestos develop MPM, suggesting the possible involvement of other risk factors. To identify the genetic factors that may modulate the risk of MPM, we conducted a gene-environment interaction analysis including asbestos exposure and 15 single nucleotide polymorphisms (SNPs) previously identified through a genome-wide association study on Italian subjects. In the present study, we assessed gene-asbestos interaction on MPM risk using relative excess risk due to interaction and synergy index for additive interaction and V index for multiplicative interaction. Generalized multifactor dimensionality reduction (GMDR) analyses were also performed. Positive deviation from additivity was found for six SNPs (rs1508805, rs2501618, rs4701085, rs4290865, rs10519201, rs763271), and four of them (rs1508805, rs2501618, rs4701085, rs10519201) deviated also from multiplicative models. However, after Bonferroni correction, deviation from multiplicative model was still significant for rs1508805 and rs4701085 only. GMDR analysis showed a strong MPM risk due to asbestos exposure and suggested a possible synergistic effect between asbestos exposure and rs1508805, rs2501618 and rs5756444. Our results suggested that gene-asbestos interaction may play an additional role on MPM susceptibility, given that asbestos exposure appears as the main risk factor