Five-year recurrence after endoscopic approach to pilonidal sinus disease: A multicentre experience.

PURPOSE: The aim of this study was to evaluate the 5-year recurrence rate of pilonidal sinus disease (PSD) after endoscopic sinusectomy and identify risk factors for recurrence. METHODS: All consecutive patients from September 2011 through December 2017 who underwent endoscopic sinusectomy at seven referral centres for pilonidal sinus treatment were retrospectively analysed from a prospectively maintained database. RESULTS: Out of 290 patients (185 males versus 105 female, with a mean age of 25.5±6.9), 73 presented recurrence at 5-year follow-up with a recurrence rate of 25.2%. The number of pilonidal sinus with pits off the midline (p = 0.001) and the mean (SD) distance from the most lateral orifice to the midline (p = 0.001) were higher in the group of patients with recurrence at 5-year follow-up. Multivariate analysis demonstrated that the position of the pits off the midline (p = 0.001) and the distance of the most lateral orifice from the midline (p = 0.001) were independent risk factors for recurrence at 5-year follow-up. Receiver operating characteristic (ROC) curve analysis showed that the distance of lateral orifice from midline predicted an 82.2% possibility of recurrence at 5-year follow-up and Youden's test identified the best cut-off as 2 cm for this variable. Out of 195 cases with the most lateral orifice less than 2 cm from the midline, 13 presented recurrence at 5-year follow-up with a recurrence rate of 6.7%. Out of 95 cases with the most lateral orifice more than 2 cm from midline, 60 showed recurrence at 5-year follow-up with a recurrence rate of 63.2%. CONCLUSIONS: This data may help guide which disease characteristics predict the optimal use of an endoscopic pilonidal sinus technique.

Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.

BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering. METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed. RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors. CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.

Use of administrative health databases to estimate incidence and prevalence of acromegaly in Piedmont Region, Italy.

PURPOSE: Recent studies from national registries have described changing patterns in epidemiology of acromegaly. Our retrospective study used administrative databases to estimate prevalence and incidence of acromegaly in the Piedmont Region, Italy. METHODS: This study was conducted in Piedmont between 2012 and 2016 on administrative health databases for inpatients and outpatients of any age. Enrollees were included if claims suggestive of acromegaly were identified in at least two of the following databases: Drug Claims Registry, Hospital Information System, Co-payment Exemption Registry and Outpatient Specialist Service Information System. RESULTS: 369 individuals (M = 146, F = 223) met our criteria. Overall incidence was 5.3 per million person years (95% CI 4.2-6.7), and prevalence was 83 cases per million inhabitants (95% CI 75-92). Mean age was 50.9 years. Both incidence and prevalence were slightly higher among women (rate ratio 1.08, prevalence ratio 1.43). Age-specific incidence was similar between sexes up to 39 years and diverged thereafter, with an increasing trend recorded among men. Prevalence was higher in women aged 40-79 years, and increased continuously up to 79 years in both sexes. CONCLUSIONS: This is the first population-based study conducted in Italy to estimate incidence and prevalence of acromegaly and results show a higher prevalence than previously reported. Although our algorithm requires proper validation, it constitutes a promising tool to describe the epidemiology of acromegaly.

Three-dimensional assessment of umbilical vein deviation angle for prediction of liver herniation in left-sided congenital diaphragmatic hernia.

OBJECTIVES: To introduce a new sonographic marker of intrathoracic liver herniation in fetuses with left-sided congenital diaphragmatic hernia (CDH). METHODS: In a consecutive series of fetuses with isolated CDH, an ultrasound volume of the fetal abdomen was acquired. On this volume, offline calculation of the angle formed by the midline of the abdomen (joining the center of the vertebral body to the abdominal insertion of the umbilical cord) and a second line joining the center of the vertebral body to the intra-abdominal convexity of the umbilical vein was carried out to give the umbilical vein deviation angle (UVDA). The UVDA was measured in a group of normal fetuses selected as controls. At follow-up, the presence of liver herniation was investigated in all cases of CDH. UVDA values were compared between the CDH group and controls, and between CDH 'liver-up' vs 'liver-down' cases. A receiver-operating characteristics (ROC) curve was constructed to identify a cut-off value of the UVDA with the highest accuracy in predicting liver herniation in the CDH group. RESULTS: Between 2009 and 2015, 22 cases of left-sided CDH were included in the study group, of which nine cases had liver herniation. Eighty-eight normal fetuses were recruited as controls. The UVDA was significantly higher in the cases vs controls (15.25 ± 7.91° vs 7.68 ± 1.55°; P < 0.0001). Moreover, the UVDA was significantly increased in CDH fetuses with liver-up vs liver-down (21.77 ± 8.79° vs 10.75 ± 2.10°; P < 0.0001). On ROC curve analysis the UVDA showed good prediction of liver herniation (area under the ROC curve, 0.94; P < 0.0001) with the best cut-off of 15.2°, yielding a sensitivity of 89% and a specificity of 100% (P < 0.0001). CONCLUSIONS: In fetuses with CDH, umbilical vein bowing may be quantified by measuring the UVDA using three-dimensional ultrasound. This sonographic marker seems to be an accurate predictor of liver herniation in left-sided CDH. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Insights into genotype-phenotype correlations from CREBBP point mutation screening in a cohort of 46 Rubinstein-Taybi syndrome patients.

The genetic basis of Rubinstein-Taybi syndrome (RSTS), a rare, sporadic, clinically heterogeneous disorder characterized by cognitive impairment and a wide spectrum of multiple congenital anomalies, is primarily due to private mutations in CREBBP (approximately 55% of cases) or EP300 (approximately 8% of cases). Herein, we report the clinical and the genetic data taken from a cohort of 46 RSTS patients, all carriers of CREBBP point mutations. Molecular analysis revealed 45 different gene alterations including 31 inactivating (21 frameshift and 10 nonsense), 10 missense and 4 splicing mutations. Bioinformatic tools and transcript analyses were used to predict the functional effects of missense and splicing alterations. Of the 45 mutations, 42 are unreported and 3 were described previously. Recurrent mutations maybe a key tool in addressing genotype-phenotype correlations in patients sharing the same defects (at the genomic or transcript level) and specific clinical signs, demonstrated here in two cases. The clinical data of our cohort evidenced frequent signs such as arched eyebrows, epicanthus, synophrys and/or frontal hypertrichosis and broad phalanges that, previously overlooked in RSTS diagnosis, now could be considered. Some suggested correlations between organ-specific anomalies and affected CREB-binding protein domains broaden the RSTS clinical spectrum and perhaps will enhance patient follow-up and clinical care.

Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene.

Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ˜55% and ˜3-5% of affected individuals, respectively. To date, only eight EP300-mutated RSTS patients have been described and 12 additional mutations are reported in the database LOVD. In this study, EP300 analysis was performed on 33 CREBBP-negative RSTS patients leading to the identification of six unreported germline EP300 alterations comprising one deletion and five point mutations. All six patients showed a convincing, albeit mild, RSTS phenotype with minor skeletal anomalies, slight cognitive impairment and few major malformations. Beyond the expansion of the RSTS-EP300-mutated cohort, this study indicates that EP300-related RSTS cases occur more frequently than previously thought (˜8% vs 3-5%); furthermore, the characterization of novel EP300 mutations in RSTS patients will enhance the clinical practice and genotype-phenotype correlations.

III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.

The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.

Mesothelioma risk after 40†years since first exposure to asbestos: a pooled analysis.

BACKGROUND: The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time. METHODS: The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM. RESULTS: The combined data consisted of 22,048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4 years (IQR 31.3-45.3). Median duration of exposure for pleural MM cases was 3.75 years (IQR 0.7-18.2). The rate and risk of pleural MM increased until 45 years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10-50 years since first exposure continued to increase. CONCLUSIONS: Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40-50 years no one survives long enough for the excess risk to disappear.

Study of socio-economic characteristics, diagnosis and outcome of women participating or not participating in mammogram screening.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer death in women. Early detection is essential to reduce cancer mortality. Studying participation in an organised breast cancer screening program is important in order to evaluate the program effectiveness. Breast screening both enables minimally invasive breast surgery and reduces cause-specific mortality. METHODS: The main objective of this study was to evaluate, through the use of a questionnaire, the influence of socio-economic characteristics (age, education, occupational status, participation in other screening programs etc.) on participation in a mammography screening program organized by the local health units (LHU) of Novara and Verbano-Cusio-Ossola, located in the Italian region of Piedmont. A sample of 500 women was identified. Eligible participants included women aged 50-69 years, resident in the area of the LHUs of Novara and Verbano-Cusio-Ossola who had been invited to participate in the screening program 2006-2007. Twenty six women were excluded, leaving 474 women in the final analysis: 23 women were unable to be contacted due to incorrect contact details and 3 women were unable to complete the questionnaire due to neurodegenerative diseases. A postal questionnaire was sent by post during 2008-2009. Two postal reminders were sent to non-responders, followed by a phone call. One group of women received an additional copy of the questionnaire with the first postal reminder and another group received only the reminder letter. The socio-personal profiles and their influence in women's participation in the screening program were evaluated. RESULTS: Among the responders, 93% of the women (348/374) received a mammogram at least once following LHU invitation for check-up. 74.1% of women got a mammogram at least once using the organized screening program, an additional 17.8% got a mammogram in a private clinic, and the type of prevention was unknown for 8.1% of the women. 25.3% began having mammogram for prevention before the age of 45. CONCLUSIONS: A screening program is a sanitary intervention of secondary prevention and the identification of the attitude towards this kind of prevention is quite complex. Some causes of non-participation in this screening program were the belief that mammogram is not necessary, fear of pain, and presence of family problems. This study obtained a higher response than expected and the data also allowed an assessment of the degree of participation of women in the prevention services, identifying that most of them carried out a mammogram using an organized screening program.

[Asbestos cement factory in Broni (Pavia, Italy): a mortality study]. / Studio di mortalità in una fabbrica per la produzione di manufatti in cemento-amianto in provincia di Pavia.

BACKGROUND: To date, no study has reported cause-specific Standardized Mortality Ratios (SMR) for asbestos-cement workers at a manufacturing establishment in Broni (Pavia, Italy). This site is among those specifically targeted by Italian Law for reclamation (SIN - Site of National Interest for remediation). OBJECTIVES: To provide cause-specific SMRs for asbestos-cement workers in the Broni (Pavia, Italy) factory, with particular regard to duration of employment and latency. METHODS: Cause-specific SMRs for asbestos-cement workers (1296 workers hired since 1/1/1950 and with follow-up period 1/1/1970-30/06/2004: 1254 males and 42 females, 545 deaths, 523 males and 22 females) were calculated using the cause-specific mortality rates for the Lombardy Region. Similarly, for pleural and peritoneal mesothelioma and lung cancer among male workers, SMRs by duration of employment and latency were calculated. RESULTS: Significantly increased SMRs were observed among male workers for pleural (SMR 17.99, 95% CI 11.75-26.36) and peritoneal (SMR 10.10, 95% CI 4.05-20.77) mesothelioma and lung cancer (SMR 1.26, 95% CI 1.02-1.55) and among female workers for pleural mesothelioma (SMR 68.90, 95% CI 8.33-248.90) and ovarian cancer (SMR 8.56, 95% CI 1.04-30.91). Only among male workers, was a significant risk trend observed for pleural mesothelioma by duration of employment and for lung cancer by latency. Significantly reduced SMRs were observed, among male workers for all causes of death, cardiovascular and respiratory diseases. CONCLUSIONS: The results of this cohort study showed increased SMRs for pleural and peritoneal mesothelioma and lung cancer among male workers and for pleural mesothelioma and ovarian cancer among female workers. These results are consistent with the literature data.

Anti-IFI16 antibodies and their relation to disease characteristics in systemic lupus erythematosus.

OBJECTIVE: Several studies have shown the presence of anti-IFI16 antibodies in systemic lupus erythematosus (SLE), Sjögren Syndrome (SjS), systemic sclerosis (SSc) and other autoimmune diseases. However, the significance of anti-IFI16 antibodies in SLE has not been fully characterized. The aim of this study was to investigate associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE. METHODS: An enzyme-linked immunosorbent assay (ELISA) kit was used to measure anti-IFI16 antibodies in the sera of 168 SLE patients, 46 patients with any type of primary glomerulonephritis (GN) and 182 healthy controls (HCs). Associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE were statistically evaluated using both univariate and multivariate analysis. RESULTS: Significantly higher anti-IFI16 titres were observed in SLE patients compared to both non-SLE GN and HCs (median levels: 270.1 U/ml vs 132.1 U/ml, p = 0.001, and 52.9 U/ml, p < 0.0001, respectively). With cut-off levels corresponding to the 95th percentile of the control population (113 U/ml), 63% of the SLE patients tested positive for anti-IFI16 autoantibodies, compared to just 24% of patients with primary non-SLE GN and 5% of HCs. The presence of anti-IFI16 antibodies inversely correlated with proteinuria (univariate analysis) and C3 hypocomplementaemia (univariate and multivariate analyses). CONCLUSIONS: The inverse correlations observed between anti-IFI16 positivity, proteinuria and C3 hypocomplementaemia suggest that anti-IFI16 antibodies do not contribute to renal inflammation in SLE; indeed they may even prevent complement consumption. Anti-IFI16 antibodies hold the potential to serve as a new biomarker of disease activity in SLE.

Air pollution and childhood leukaemia: a nationwide case-control study in Italy.

OBJECTIVES: Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. METHODS: The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998-2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. RESULTS: Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m(3) (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. CONCLUSIONS: Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

Electromagnetic navigation bronchoscopy and rapid on site evaluation added to fluoroscopy-guided assisted bronchoscopy and rapid on site evaluation: improved yield in pulmonary nodules.

AIM: Electromagnetic navigation bronchoscopy (ENB) was reported to increase diagnostic yield in pulmonary nodules (PNs). The aim of this study was to assess if rapid on site evaluation (ROSE) associated with ENB could improve diagnostic accuracy in PNs after non-diagnostic fluoroscopy-guided bronchoscopy added to ROSE. METHODS: Forty patients with PNs suspected for lung cancer underwent to ENB + ROSE after non-diagnostic Fluoroscopy-guided Bronchoscopy + ROSE. Each lesion was studied with reference to size, location, presence of bronchus sign on CT. All lesions were sampled by needle and brush; if negative, by forceps and bronchoalveolar lavage. All patients were followed-up until achievement of definitive diagnosis. RESULTS: Twenty-nine out of 41 lesions (70.7%) had a definitive diagnosis. ENB sensitivity for malignancy was 76.5%, with higher rate in presence of bronchus sign on CT (86.2%) and in case of lesions located in the upper and middle lobes (87.5%). CONCLUSION: ENB is a useful tool in the evaluation of PNs. High diagnostic accuracy may be related to sampling (transbronchial needle aspiration), ROSE, location and presence of bronchus sign.

Epidemiology of hepatitis D virus (HDV) infection in an urban area of northern Italy.

OBJECTIVES: The introduction of vaccination against hepatitis B initially reduced the number of HBV (hepatitis B virus) and HDV (hepatitis delta virus) infections, but the decreasing trend of HDV infection seems to have stopped. The aim of this study was to assess the prevalence of HDV infection in the general population living in the catchment area of Legnano Hospital in northern Italy. METHODS: Of the 22,758 subjects tested in 2007-2008, the 488 who were HBsAg (hepatitis B surface antigen)-positive [including 107 (21.9%) of non-Italian origin] were subsequently tested for anti-HDV antibodies. RESULTS: Of the 488 subjects who tested positive for HBsAg, 24 (4.9%) were anti-HDV positive, all aged between 30 and 60 years. The difference in prevalence between males (7.1%) and females (1.9%) was statistically significant (p < 0.05), but not that between Italian (5.0%) and non-Italian patients (4.7%). The differences in anti-HDV seropositivity between the patients with acute (0%) and chronic infections (6.3%), and between the incident (2.5%) and prevalent cases (7.4%), were not statistically significant, but there was a significant difference (p < 0.01) between those with asymptomatic (2.1%) and clinically symptomatic infections (10.3%). Intravenous drug abuse was the main source of infection. CONCLUSIONS: In the catchment area of our hospital, the prevalence of HDV infection does not seem to be due to patients of non-Italian origin, but to Italian patients who are not vaccinated against HBV and who survived the HDV epidemic of the 1970s and 1980s. Nevertheless, the increase in the number of immigrants from non-EU countries in recent years is soon likely to lead to a change in the epidemiology of HDV.

The interactions of age, sex, body mass index, genetics, and steroid weight-based doses on tacrolimus dosing requirement after adult kidney transplantation.

PURPOSE: The aim of this study was to evaluate the effect of different clinical covariates on tacrolimus dose requirements in adult kidney transplant patients with a specific focus on drug interactions. PATIENTS: Tacrolimus dosing requirement, normalized by drug levels and expressed as the concentration/dose (C/D) ratio as a surrogate index of tacrolimus bioavailability, was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very-small, in very fast, fast, slow, and very slow metabolizers, respectively. Steroid weight-based doses were analyzed instead of fixed doses, and genetic analysis of cytochrome P450 (CYP) 3A5*1/*3 and multi-drug resistance 1 (MDR1) C3435T and C1236T polymorphisms were performed RESULTS: Multivariate analysis on 450 adult transplant patients identified six risk factors for being slow metabolizers and therefore requiring small tacrolimus doses: male sex (OR 1.615, p = 0.020); age >60 years (OR 2.456, p = 0.0005); body mass index ≥ 25 (OR 1.546, p = 0.046), hepatitis C virus positivity (OR 2.800, p = 0.0004); low steroid dose <0.06 mg/kg (OR 3.101, p < 0.0001). Patients with a small tacrolimus requirement were at increased risk for multiple infections (OR 1.533, p = 0.0008) and higher systolic blood pressure (OR 1.385, p = 0.022) and showed a significant association with the CYP3A5*3/*3 genotype adjusted by MDR1 polymorphisms C3435T and C1236T (OR 8.104, p = 0.0001). CONCLUSIONS: Our results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacrolimus requirement. As the tacrolimus dosing requirement increases with increasing tacrolimus clearance through concomitant steroid use, undesirable changes in tacrolimus levels may occur when steroid doses are tapered, predominantly in slow metabolizers. This often neglected drug interaction has to be monitored to optimize tacrolimus exposure in kidney transplant patients.

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.

Value of autopsy in renal malformations: comparison of clinical diagnosis and post-mortem examination.

BACKGROUND AND AIM: This 6-year retrospective study reports 14 cases of renal malformations, observed in foetuses and newborns. The objective was to evaluate the usefulness of post-mortem examination in cases of renal malformations by a comparison of the post-mortem findings with clinical diagnosis. METHODS: This study included laboratory tests, ultrasonography, karyotype and detailed pathological evaluation of the foetuses and newborns by external, macroscopic, microscopic and placental examination. RESULTS: The results of post-mortem examination were of paramount importance: they disclosed renal malformations escaped on prenatal studies (42,86%), provided extensive additional informations (50%), or confirmed the diagnosis hypothesis (7,14%). CONCLUSIONS: Thus, this study confirmed the need of pathological examination for foetuses and newborns, after medical abortion and neonatal death. The pathologist's contribution to the multidisciplinary management of prenatal or postnatal abnormalities is important in particular for further genetic counseling. (www.actabiomedica.it).