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Background. High blood pressure (BP) poses a major risk for cognitive decline. Aim of the study was to highlight the relationship between cognitive assessment scores and an effective therapeutic BP control. Methods. By medical visit and ambulatory BP monitoring (ABPM), we studied 302 treated hypertensives, subdivided according to office/daytime BP values into 120 with good (GC) and 98 poor (PC) BP control, 40 with “white coat hypertension” (WCH) and 44 a “masked-hypertension” phenomenon (MH). Patients underwent neuropsychological assessment to evaluate global cognitive scores at the Mini Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) and attention/executive functions (Delayed Recall, Digit Span Forwards, Digit Span Backwards, Selective Attention, Verbal Fluency, Stroop Test and Clock Drawing). Carotid intima-media thickness (IMT) served as the index of vascular damage. Results. There were no differences among the groups in terms of gender, age, education, metabolic assessment, clinical history and hypertension treatment. GC presented lower office and ambulatory BP values and IMT. PC performed worse than GC on global executive and attention functions, especially executive functions. In PC, office systolic BP (SBP) was significantly associated to the MMSE and FAB scores and, in particular, to Verbal Fluency, Stroop Errors and Clock Drawing tests. Office diastolic BP (DBP) was associated to Selective attention, nocturnal SBP to Digit Span backwards and Verbal Fluency. Worse cognitive assessment scores were obtained in WCH than GC. Conclusions. The findings showed that in adult treated hypertensives, a poor BP control, as both doctor's office and daytime scores, is associated to impaired global cognitive and especially executive/attention functions.

Postoperative infections are a concern, especially in total knee and total hip arthroplasty. We evaluated the air quality in orthopaedic operating theatres in southeastern Italy to determine the level of bacterial contamination as a risk factor for postoperative infection. Thirty-five hospitals with operating theatres focused on total knee and total hip arthroplasty participated. We sampled the air passively and actively before surgeries began for the day (at rest) and 15 min after the surgical incision (in operation). We evaluated bacterial counts, particle size, mixed vs turbulent airflow systems, the number of doors, number of door openings during procedures and number of people in the operating theatre. We found no bacterial contamination at rest for all sampling methods, and significantly different contamination levels at rest vs in operation. We found no association between the number of people in the surgical team and bacteria counts for both mixed and turbulent airflow systems, and low bacterial loads, even when doors were always open. Overall, the air quality sampling method and type of ventilation system did not affect air quality.

Hypertension and metabolic disorders, attended by impaired microcirculation, represent major risk factors for cerebrovascular impairment, as well as being individual components of the metabolic syndrome (MetS). Aim of the study was to establish whether mild hypertensives, aged ≤65years, may be affected by progressive microvascular damage impairing cerebrovascular perfusion, related to a progressive clustering of MetS components.Twenty-two normotensives with no MetS component (NTN-0), 29 hypertensives with no (HTN-0), 30 with one (HTN-1), 29 with two (HTN-2), 27 with three (HTN-3), 25 with all four (HTN-4) MetS components, were recruited. The study required office and twenty-four hour ambulatory blood pressure monitoring and video capillaroscopy. Functional (fCD), anatomical (aCD) and recruited (RECR) phalangeal skin capillarity were assessed. Cerebral vasodilatory reserve was measured by the breath-holding index (BHI), using transcranial Doppler, in HTN-1 and HTN-2 with MetS.The fCD and aCD were reduced in hypertensives and progressively reduced in those with MetS, while RECR was also impaired. BHI was lower in HTN-2 than in HTN-1 (p0.001). BHI was correlated with fCD in HTN-1 (.396, p: .046), HNT-2 (.497, p: .011), and with aCD in HTN-2 (.494, p: .012), by partial Pearson test.The findings show that hypertensives exhibit an increasing microvascular rarefaction with MetS progression and that an impaired cerebral perfusion occurs when the MetS is established. The data underline the importance of preventing MetS in mild hypertensives, as it causes microvascular damage and impairs cerebral arterial perfusion.

Scattone A, Serio G, Marzullo A, Nazzaro P, Corsi F, Cocca M P, Mattoni M, Punzi A, Gentile M, Buonadonna A L & Pennella A (2012) Histopathology60, 472–481 High Wilms’ tumour gene (WT1) expression and low mitotic count are independent predictors of survival in diffuse peritoneal mesothelioma Aims: To evaluate the use of the Wilms’ tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM). Methods and results: Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High-grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (>25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05–3.71] versus 31.5 months (95% CI: 20.4–42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively). Conclusions: Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

BACKGROUND Hypertension and diabetes are significantly associated with insulin resistance (IR), which could affect the vasodilatory capacity and microcirculation. The aim of the study was to verify whether IR is associated with a reduced microvascular blood flow in normoglycemic mild hypertensives. METHODS Eighty-four untreated grade-1 hypertensives were equally divided, according to the IR homeostasis model assessment (HOMA) index, into three groups: IR-Low = 2.16 +/- 0.09 vs. IR-Medium = 3.77 +/- 0.09 vs. IR-High = 7.08 +/- 0.68 (P < 0.001) with similar sex distribution, office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and history of hypertension. They underwent ambulatory blood pressure monitoring (ABPM) and a laboratory stress session, during which blood pressure (BP), heart rate (HR), and skin blood flow (Laser Doppler) were taken on the forehead (LDF) and the hand (LDH), where the neuroadrenergic control of the microvascular blood flow is higher. Reactivity was calculated as "area-under-the-curve" (AUC) during arithmetic and cold pressor tests. Postischemic LDH served as the index of endothelial microcirculatory damage. RESULTS ABPM confirmed the diagnosis of hypertension, but IR-High patients showed a reduced nighttime BP fall. They also demonstrated reduced LDH-AUC and LDF-AUC although BP-AUC and HR-AUC reactivity were similar. Postischemic LDH was lower in the IR-High group (P < 0.05), and the postischemic LDH change was progressively impaired in both IR-Medium and IR-High patients (P < 0.001). LDH-AUC (-0.305, P = 0.007) and postischemic LDH at 30 s (-0.217, P = 0.059) and 60 s (-0.248, P = 0.030) during hyperemia were associated with HOMA. Multiple regression analysis, with HOMA as the dependent variable, showed that BMI (beta = 0.336, P < 0.001) and LDH (beta = -0.239, P < 0.001), LDH-AUC (beta = -0.296, P < 0.01) and postischemic LDH change (beta = -0.321, P < 0.001) entered the equation. CONCLUSIONS The findings suggest that IR is associated with functional microvascular constrictive impairment in normoglycemic mild hypertensives.

During brain development and blood-brain barrier (BBB) differentiation the expression of P-glycoprotein (P-gp) may complement the protective function of the placental barrier against xenobiotic substances. To establish an immunohistochemical procedure for P-gp detection, different anti-P-gp monoclonal antibodies were first tested on a fibrosarcoma cell line and colonic carcinoma tissue. The protocol was then tested on adult human brains as a BBB-P-gp tissue-specific control and for double labeling with anti-P-gp and the astroglia marker glial fibrillary acidic protein (GFAP). The protocol was then used to analyze the expression and localization of P-gp in human fetuses during cerebral cortex formation. At the earliest examined stage, 12 weeks of gestation (wg), P-gp was detectable as diffuse cytoplasmic labeling of the endothelial cells lining the primary cortex microvessels. At 18 wg, a punctate P-gp staining pattern was detected on cortex and subcortical vessels and on their side branches. At 22 wg, P-gp staining was linear and concentrated on endothelial cell membranes. In all examined ages, GFAP-positive radial glial cells and astrocytes did not stain for P-gp, even at their perivascular processes, whereas faint P-gp labeling was seen on vimentin-reactive radial glia at the earliest examined fetal age. At midgestation, P-gp colocalized with caveolin-pY14 on the abluminal endothelial cell membrane. These results demonstrate that P-gp is expressed early during human cerebral cortical microvessel development, and suggest that at midgestation there may be efflux activity that is regulated by interactions with the caveolar endothelial cell compartment.

Background Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency. Method Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours. Results In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/μV at baseline to 62 ± 30 ml/μV at 48 hours (p 2O/μV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38– 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78– 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04). Conclusion After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not. Trial registration ClinicalTrials.gov study registration: NCT0247317, 06/11/2015.

To assess the performance of different ovarian reserve tests for predicting the total numbers of oocytes retrieved and mature oocytes.A retrospective study was performed on 71 women undergoing their first IVF/intracytoplasmic sperm injection treatment. Basal ovarian reserve screening was performed on days 2-3 of a spontaneous cycle. Patients were down-regulated with the GnRH agonist, whereas ovarian stimulation was carried out with recombinant FSH, starting from day 2 to 3 of the cycle. The main outcome measures were the numbers of oocytes retrieved and mature oocytes.The total number of oocytes was positively correlated with AFC (p0.0001) and E(2) levels post-GnRH (p0.004), whereas there was an inverse correlation with age (p0.0001). The number of mature oocytes also correlated with AFC (p0.008) and E(2) levels post-GnRH (p0.009), and inversely with age (p0.0004). Univariate linear regression of square root of number of oocytes (SQNO) shows that acceptable predictors of number oocytes, based on model significance and R(2) are AFC (R(2)=0.215), age (R(2)=0.24) and E(2) variation (R(2)=0.09). The following model is proposed to predict the number of mature oocytes: ln(MO)=ln(NO)-2.09+0.028 AGE+0.03 BMI.The number of antral follicles and patient age appear to be good markers of ovarian response in IVF treatments. Additional information is provided by stimulated E(2) levels.

Gastric carcinoma is one of the major causes of cancer mortality worldwide. Early detection results in excellent prognosis for patients with early cancer (EGC), whereas the prognosis of advanced cancer (AGC) patients remains poor. It is not clear whether EGC and AGC are molecularly distinct, and whether they represent progressive stages of the same tumor or different entities ab initio. Gene expression profiles of EGC and AGC were determined by Affymetrix technology and quantitative polymerase chain reaction. Representative regulated genes were further analysed by in situ hybridization (ISH) on tissue microarrays. Expression analysis allowed the identification of a signature that differentiates AGC from EGC. In addition, comparison with normal gastric mucosa indicated that the majority of alterations associated with EGC are retained in AGC, and that further expression changes mark the transition from EGC to AGC. Finally, ISH analysis showed that representative genes, differentially expressed in the invasive areas of EGC and AGC, are not differentially expressed in the non-invasive areas of the same tumors. Our data are more directly compatible with a progression model of gastric carcinogenesis, whereby EGC and AGC may represent different molecular stages of the same tumor. Finally, the identification of an AGC-specific signature might help devising novel therapeutic strategies for advanced gastric cancer.

A comparative evaluation between the Joel-Cohen incision and its modification for the Stark's cesarean section (CS).In a retrospective study, 477 women who underwent a Stark's CS were evaluated: 204 with the Joel-Cohen incision (JC) and 273 with a modified Joel-Cohen incision (MJC). All patients were checked for the following parameters: febrile morbidity, the need for painkillers, duration of hospital stay, and ultrasound examination for blood collection (BC) on the third postoperative day. The collections, when diagnosed were divided into three groups: (1) in the abdominal wall, (2) in the pouch of Douglas, and (3) in the lower uterine segment (LUS). Those included in the study were low-risk primiparae at term, presenting for CS for breech presentation, macrosomia, and on demand, and who had combined spinal-epidural anesthesia. Statistical evaluation was performed using SAS/V12 software.There were no statistical differences between the two groups with regard to febrile morbidity, duration of need for painkillers, and hospital stay. Statistically more blood collections were found in the MJC incision group (5.4% in the abdominal wall, 12.4% in the pouch of Douglas, and 11.7% in the LUS) than in the classical JC incision group (3.9% in the abdominal wall, 10.2% in the pouch of Douglas, and 8.8% in the LUS), however without any clinical significance.The routine use of the classical JC incision during the Stark's CS seems to be more rational, and causes fewer blood collections.

Background The increase in costs related to the diagnosis and treatment of chronic-degenerative diseases requires a better knowledge of the true care pathway of patients. The study objective was to explore, using multi-state modeling, how analyses of drug prescriptions and data obtained from hospital discharge sheets can be used in combination to build a model of patients health care pathway in a non experimental setting. The model was applied to Chronic Obstructive Pulmonary Disease (COPD). Methods Based on the GOLD guidelines, access to hospitalization for COPD and prescription pharmaceuticals were awarded to seven transients states theoretically progressive. The intensity of transition were estimated with the non-parametric method proposed by Aalen and Johansen for multi-state Markov models non-homogeneous in time. Results The COPD patients included in the study are 111190. Patients admitted with a diagnosis of non acute COPD had a growing probability over time of needing prescriptions for inhaled corticosteroids (ICS) or the set combination of long-acting beta-agonists (LABA) and ICS; they also had a rising probability of an exacerbation. The use of ICS alone or in combination with LABA delays a hospital admission for acute respiratory failure by about 6 months, as compared to short-acting beta-agonists or anticholinergics. Conclusion The probabilities of a transition and their distribution in relation to time, sex, age and clinical status can be a helpful tool for those operating in the health care sector, who are called upon to carry out decisions from the standpoints of both efficacious clinical management and an efficient use of resources.

The purpose of this study was to evaluate the prevalence of intestinal parasites in 277 healthy subjects in the city of Mamuras (Albania, South Eastern Europe) and the correlation between parasitic infections and possible risk factors. Faecal samples collected with sodium-acetate-formalin fixative were concentrated by formalin ethylacetate sedimentation and examined as wet mounts, permanent stains and by anti-Giardia/Cryptosporidium fluorescent antibodies. Data concerning age, sex, level of education, availability of piped water, number of people living in the same house, and residence in rural or urban area were collected for each subject. Statistical analysis was performed by chi-square test and regression logistic analysis. The overall prevalence of intestinal parasites was 183/277 (66.06%). In particular, pathogenic protozoa or helminths were found in 67 subjects (24.18%), including Trichuris trichiura in 34 (12.27%), Giardia duodenalis in 31 (11.19%), Hymenolepis nana in 5 (1.8%), Ascaris lumbricoides in 3 (1.08%). A significant correlation was observed only between parasite colonization and older age and between Trichuris trichiura infection and residence in rural areas.

Background.Salivary glands tumours are uncommon, frequently benign lesions, prevalently located in the parotid gland (80%). Surgical decision making is based on the patient’s history, examination findings, imaging and fine needle aspiration (FNA). FNA is a pre-operative method with good ability in detecting malignancy. During surgery, therefore, Frozen section (FS) can differentiate benign lesions from malignant tumours, to reduce incorrect treatments, to increase the chances of conservative surgery and to better evaluate surgical margins. The aim of our study is to demonstrate the accuracy of the FS procedure in surgery of the salivary glands and to stress the need for dedicated pathology units specialized in lesions of the oral cavity.Methods. The study included 499 patients who underwent surgery from May 2005 and October 2014. An intra-operative frozen section procedure was done for 288 of them. All frozen sections were compared with the final results. The cases were classified by site, nature of the lesion and histotype, according to the WHO classification. Comparison was made between the intra-operative and the definitive diagnosis.Results.Of the 288 FS procedures, 259 were for neoplastic lesions, 199 of which benign and 60 malignant, and 29 for non-neoplastic lesions. Of the 259 neoplastic FS results, 2 were shown to be false positives and 2 were diagnosed as different malignant types. Of the 29 non-neoplastic FS results, 4 were false negatives.Conclusions.Our results showed that the accuracy of frozen section procedure is 98% for salivary glands tumors. The highest concordance between frozen section and the definitive diagnosis was for inflammatory processes (99%), pleomorphic adenoma (98%), Warthin’s tumor (97%) and malignant neoplasms (96%). In conclusion, based on these findings, frozen section of the salivary glands may be proposed as a routine procedure and should be used in decision-making.

Epithelial hyperplastic laryngeal lesions (EHLL) are associated, with a varying degree of "epithelial risk"- to develop invasive carcinoma. Several classifications have been proposed but none has received a total agreement. The 1999 Ljubljana classification distinguished four grades: simple, abnormal and atypical hyperplasia and in situ carcinoma (ISC). The first two grades are considered benign lesions; the ISC is the malignant lesion, while the atypical hyperplasia is considered a "risky lesion". This is characterized by alterations of epithelial cells towards malignancy, but not to the extent to be found in carcinoma cells. Such characteristics refer to cytomorphological (e.g., nuclear hyperchromatism, nucleoli, increased nuclear/cytoplasmic ratio) and architectural (e.g. stratification, orientation, maturation) features. In the Ljubljana scheme, nuclear pleomorphism is one of the most important features. We wanted to improve the importance of nuclear pleomorphism in the basal cells layer in different classes of EHLL using morphometrical analysis. We studied 8 cases of simple hyperplasia, 10 of abnormal hyperplasia, 10 of atypical hyperplasia and 8 of ISC using the software SAM (Shape Analytical Morphometry). The results were submitted to univariate statistical analysis. Nuclear dimensions (maximum diameter, perimeter and area) showed a progressive increase from simple to atypical hyperplasias to ISC, while abnormal hyperplasia showed the lowest values. On the contrary, analytical parameters related to nuclear contour irregularities and asymmetries showed their highest values in abnormal hyperplasia nuclei. There were no significant differences between atypical hyperplasia and ISC, while it was possible to differentiate abnormal hyperplasia from the others. In conclusion basal nuclei of atypical hyperplasia and ISC are similar so that other cytological and morphological architectural parameters are necessary to distinguish the two lesions. Abnormal hyperplasia seems to be the biological category of 'proliferative " benign laryngeal epithelium; simple hyperplasia refers to "stable" - irritative epithelium.

We describe a family of three sisters affected by malignant mesothelioma (MM) (2 pleural and 1 peritoneal) and one brother affected by pleural plaques. All members of the family had been subjected to previous asbestos exposure of environmental-residential type. For 13 years, from 1951 to 1964, their housing was provided by the father's employer, an asbestos cement factory, and the factory warehouse was on the ground floor of the building they lived in. DNA extracted from paraffin-embedded MM samples was used to search for chromosomal alterations by a comparative genomic hybridization (CGH) method. In two cases, a loss at 9p was found to be the only change. The loss at 9p is a frequent event in malignant mesothelioma and the fact that this anomaly was diagnosed in two sisters as the only alteration suggests that this region may be the site of one or more oncosuppressor genes that could play an important role in the development of MM and in inducing greater genetic susceptibility to the carcinogenic effects of asbestos.

The aim of this work was to evaluate the accuracy of vacuum-assisted biopsy by comparing it with frozen biopsy. 141 stereotaxic biopsies were performed by Mammotome (Ethicon Endo-Surgery, Hamburg) from January 2000 to March 2001. Biopsies were performed for microcalcifications (n = 105, 74.5%), irregular opacities (n = 20, 14.2%), regular opacities (n = 6, 4.2%), stellate lesions (n = 10, 7.1%). Histological analysis showed 85 (60.3%) benign lesions, 46 (32.6%) malignant lesions including (21 cases of carcinoma in situ and 25 invasive carcinomas) and 10 (7.1%) atypical lesions. All malignant lesions were subjected to surgery. In three cases (1 in situ and 2 invasive), core biopsy was excisional and no residual lesion was observed. Two of the carcinomas in situ revealed invasive features on the surgical biopsy. One of the atypical lesions was underestimated and the final diagnosis was "well differentiated carcinoma in situ." Only three of benign lesions underwent surgery after Mammotome biopsy. Among the 55 frozen-section biopsies of mammographically detected breast lesions performed in the same period, were one false-positive and 3 false-negative cases, while in 4 cases the diagnosis was deferred after paraffin embedding. Our results confirmed Mammotome biopsy as an effective alternative and a more reliable method than frozen-section examination.

Malignant deciduoid mesothelioma of the pleura: report of two cases with long survival Aims: To present two rare cases of malignant mesotheliomas with deciduoid features arising in the pleura, both with long survival. Methods and results: These two cases of deciduoid mesotheliomas were observed in adult patients (one 73-year-old male and one 23-year-old female). Only the male had a history of occupational asbestos exposure, whereas the woman had a history of familial mesothelioma. A deciduoid morphology was predominant and focal areas with tubular-papillary features were noted. The tumour cells were positive for cytokeratins, HMBE-1, calretinin, EMA and mitochondrion antibodies. The follow-up data did not suggest a particularly poor prognosis; the mean survival observed was 23 months (17 and 39 months, respectively). Conclusions: This deciduoid mesothelioma histological subtype does not appear to represent an unfavourable prognostic category.

Aims and Background Computed tomography (CT) does not represent the primary method for the evaluation of breast lesions; however, it can detect breast abnormalities, even when performed for other reasons related to thoracic structures. The aim of this study is to evaluate the potential benefits of 320-row multidetector CT (MDCT) in evaluating and differentiating incidentally detected breast lesions by using vessel probe and 3D analysis software with net enhancement value. Methods and Study design Sixty-two breast lesions in 46 patients who underwent 320-row chest CT examination were retrospectively evaluated. CT scans were assessed searching for the presence, location, number, morphological features, and density of breast nodules. Net enhancement was calculated by subtracting precontrast density from the density obtained by postcontrast values. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of CT were calculated for morphological features and net enhancement. Results Thirty of 62 lesions were found to be malignant at histological examination and 32 were found to be benign. When morphological features were considered, the sensitivity, specificity, accuracy, PPV, and NPV of CT were 87%, 100%, 88%, 100%, and 50%, respectively. Based on net enhancement, CT reached a sensitivity, specificity, accuracy, PPV, and NPV of 100%, 94%, 97%, 94%, and 100%, respectively. Conclusions MDCT allows to recognize and characterize breast lesions based on morphological features. Net enhancement can be proposed as an additional accurate feature of CT.

Our purpose was to retrospectively evaluate the incidence and morphologic features of diabetic mastopathy in a group of patients with diabetes, searching for specific sonographic characteristics of diabetic mastopathy.One hundred twenty diabetic patients underwent breast clinical examination, mammography, and sonography. All detected breast lesions were confirmed histopathologically.Breast lesions were found in 11 of the 120 patients (9%), including two cases of invasive ductal carcinomas and nine cases of diabetic mastopathy. In seven of those nine cases (77%), diabetic mastopathy appeared as a hypoechoic solid mass with irregular margins, inhomogeneous echotexture, and marked posterior shadowing. In the other two cases (23%), it appeared as a mildly inhomogeneous, hypoechoic solid mass.Diabetic mastopathy is a diagnostic challenge and needs to be suspected in all patients with diabetes mellitus. Imaging features are nonspecific and highly susggestive on breast sonography in most cases. Core-needle biopsy confirmation remains mandatory for a definitive diagnosis.

TGF-β1 was inversely correlated with E-cadherin but significantly correlated with VEGF. VEGF and AFP had a low coefficient value but statistically significant. A significant correlation was found between E-cadherin and MMP2. In conclusion, TGF-β and E-cadherin are inversely correlated in HCC patients' sera and not related to the BCLC classification nor survival but rather to the biological properties of the tumor.

Objective To obtain a nomogram of the clivus–supraocciput angle as a basis for the diagnosis of Chiari II malformation in fetuses with ventriculomegaly. Methods A cross-sectional study was undertaken on 310 normal pregnant women of 16–34 weeks' gestation. A mid-sagittal section of the fetal skull was obtained and the angle between the clivus and the supraocciput was measured. Forty-four fetuses with ventriculomegaly due to various causes (13 Chiari II malformation, 12 dysgenesis of the corpus callosum, 7 aqueductal stenosis, 6 borderline ventriculomegaly, 3 Dandy–Walker malformation, 2 porencephaly, 1 schizencephaly) were also included in the study and the values of the angle found in the pathological cases were compared with those found in the normal population. Results The clivus–supraocciput angle did not change during gestation and was almost constant with an average value of 79.3 ± 6°. All cases of Chiari II malformation showed a value below the 5th centile of our nomogram. Conclusions The evaluation of the posterior fossa and particularly the measurement of the clivus–supraocciput angle is a useful parameter to differentiate the various causes of fetal ventriculomegaly and particularly to recognize Chiari II malformation. Copyright © 2001 International Society of Ultrasound in Obstetrics and Gynecology

Objective : To investigate the response of HIV-associated severe thrombocytopenia (STP) to highly active antiretroviral therapy (HAART) including protease-inhibitors. Methods : In this retrospective study, 15 patients with HIV-associated STP (platelet count 9 /l), mostly antiretroviral experienced (13/15), underwent HAART for at least 6 months (median 21; range 6–41 months) during which the platelet (PLT) count and plasmatic HIV-RNA were monitored. The PLT response was compared to that observed in 19 patients previously treated with zidovudine (AZT) monotherapy. Results : HAART induced a significant increase in the PLT count (χ 2 =10.53, P =0.01) within the third month which was sustained up to the sixth month of therapy. No STP relapse was observed among eight PLT responders followed for longer than 6 months (median 27; range 7–41 months). The PLT increase after HAART was similar to that observed with AZT monotherapy, but a greater number of HAART patients were antiretroviral-experienced. HAART determined a PLT response in 10/13 subjects whose thrombocytopenia had not improved after previous AZT monotherapy. After 6 months of HAART, a complete platelet response occurred more frequently in patients with undetectable plasma HIV-RNA levels ( P =0.01). Conclusions : HAART induces a sustained PLT response in HIV-associated STP, even in antiretroviral-experiencedsubjects and in those with AZT-resistant thrombocytopenia. An undetectable plasma HIV viraemia induced by HAART is necessary for STP recovery.

Aim To compare the diagnostic accuracy of fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) in patients with USdetected breast lesions. Patients and methods Between September 2011 and May 2013, 3469 consecutive breast US examinations were performed. 400 breast nodules were detected in 398 patients. 210 FNACs and 190 CNBs were performed. 183 out of 400 (46%) lesions were surgically removed within 30 days form diagnosis; in the remaining cases, a six month follow up US examination was performed. Sensitivity, specificity, diagnostic accuracy, positive predictive (PPV) and negative predictive (NPV) values were calculated for FNAC and CNB. Results 174 out of 400 (43%) malignant lesions were found while the remaining 226 resulted to be benign lesions. 166 out of 210 (79%) FNACs and 154 out of 190 (81%) CNBs provided diagnostic specimens. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 97%, 94%, 95%, 91% and 98% were found for FNAC, and values of 92%, 82%, 89%, 92% and 82% were obtained for CNB. Sensitivity, specificity, diagnostic accuracy, PPV and NPV of 97%, 96%, 96%, 97% and 96% were found for FNAC, and values of 97%, 96%, 96%, 97% and 96% were obtained for CNB. Conclusion FNAC and CNB provide similar values of diagnostic accuracy.

We describe a unique case of brain metastases presenting as first symptom of a malignant mesothelioma (MM). MM is a highly aggressive tumor of the serous membrane that is generally believed to be rarely metastasizing. Recently, the reports of long surviving cases and larger literature reviews have suggested that cerebral metastases are not so uncommon. An extensive histochemical and immunohistochemical panel is needed to achieve a correct differential diagnosis, especially in the epithelioid type. Pathologists should be aware that brain metastases could have a mesothelial origin.

In the histological grading of oral squamous cell carcinoma (OSCC) nuclear features are very important. Nevertheless evaluation is usually performed in a subjective and not highly reproducible way. The aim of this work was to investigate the relationship between nuclear shape and survival in 30 cases of carcinoma of the tongue. All the patients were divided into two groups: short-term survival and long-term survival. Twenty nuclei for each tumour were submitted to a morphometrical study by the shape analytical morphometry (SAM) software system. It was thus possible to evaluate not only nuclear dimensions but also nuclear contour irregularities and nuclear shape asymmetries. Multivariate discriminant analysis (MDA) of the quantitative parameters obtained by the morphometrical study distinguished the patients of the two groups with only a 10% error; moreover successful cluster analysis was performed by using Fourier parameters. Both these sets of results were achieved mainly owing to the parameters for contour irregularities.

to compare ultrasound (US) and autopsy findings of fetal malformations in second trimester terminations of pregnancy to evaluate the degree of agreement between US and fetal autopsy.in this study, all second trimester termination of pregnancy between 2003-2010 were considered. US and autopsy findings were compared and all cases were classified into five categories according to the degree of agreement between US and pathology (A1: full agreement between US and autopsy; A2: autopsy confirmed all US findings but revealed additional anomalies 'rarely detectable' prenatally; B: autopsy demonstrated all US findings but revealed additional anomalies 'detectable' prenatally; C: US findings were only partially demonstrated at fetal autopsy; D: total disagreement between US and autopsy).144 cases were selected. In 49% of cases there was total agreement between US and autopsy diagnosis (A1). In 22% of cases additional information were about anomalies 'not detectable' by US (A2). In 12% of cases autopsy provided additional information about anomalies not observed but 'detectable' by US (B). In 13% of cases some anomalies revealed at US, such as valve insufficiencies, pericardial and pleural effusions, were not verified at autopsy (C). Total lack of agreement was noted only in 4% of cases (D). Main areas of disagreement concerned cardiovascular, CNS and complex malformations. The degree of agreement was higher if malformations were diagnosed in a tertiary center.this study shows an overall high degree of agreement between definitive US and autopsy findings in second trimester termination of pregnancy for fetal malformations. Autopsy reveals to be the best tool to diagnose malformations and often showed other abnormalities of clinical importance not detected by US, but sometimes also US could provide additional information about functional anomalies because US is a dynamic examination.

To evaluate the use of the Wilms' tumour gene (WT1) marker and histomorphological parameters as indicators of prognosis in malignant peritoneal mesothelioma (MPM).Histological samples of 31 MPM were stained immunohistochemically for the WT1 protein. The results were quantified by recording the number of stained nuclei, and then correlated with patient survival. Statistical correlation was evaluated for tumour histotype, mitotic count (MC), nuclear grade (NG), necrosis, lymphoid response (grade of inflammation) and desmoplasia with regard to survival. High-grade histology (solid epithelioid, pure sarcomatoid or biphasic tumours), high NG, MC more than five per 10 per high-power field (HPF), necrosis and desmoplasia were associated with a significantly worse prognosis. Patients with MPM with low WT1 expression (≤25% of positive cells) survived for a significantly shorter time compared to those with high WT1 expression (25% of positive cells) (P = 0.0001). The 50% survival time of subjects with low WT1 expression was 2.9 months [95% confidence interval (CI): 2.05-3.71] versus 31.5 months (95% CI: 20.4-42.5) for those with high WT1 expression. On multivariate analysis, WT1 and MC were found to be associated independently with survival (P = 0.002; P = 0.005, respectively).Our study suggests that low WT1 expression and high MC may be indicative of an unfavourable prognosis in patients with advanced malignant peritoneal mesothelioma.

Background: Autologous stem cell transplantation (ASCT) generally provides good results in Hodgkin’s lymphoma (HL). We studied a high-dose chemotherapy regimen based on thiotepa, etoposide and carboplatin (TECA).Methods: Fifty-eight patients with advanced HL were treated with thiotepa, etoposide and carboplatin for transplant induction.Results: The overall response rate was 79·3% (39 CR: 67·2%; and 7 PR: 12·1%); 12 patients (20·1%) were non-responders. The 5-year overall survival rate was 77·6%; five initially responder patients relapsed within the first 5 years of follow-up and underwent salvage therapy.Conclusion: The TECA conditioning regimen for ASCT in HL results in a good anti-HL effect, positive response to treatment and high 5-year overall survival rate. It was also well tolerated and did not induce excessive toxicity, suggesting that TECA may be a very useful conditioning regimen for HL.

High-dose chemotherapy conditioning regimens followed by autologous stem cell transplantation generally provide good results in non-Hodgkin lymphoma. We have evaluated the effects of a high-dose regimen comprising thiotepa, etoposide and carboplatin. After debulking and mobilization with high-dose cyclophosphamide or other schedules, forty-five patients at various disease stages were conditioned with thiotepa, etoposide and carboplatin prior to autologous stem cell transplantation. The overall response rate was 77.8% (30 CR, 66.7%; 5 PR, 11.1%). Ten patients (22.2%) did not respond. Two patients (4.4%) died from transplant-related complications. The mean 5-year overall survival was 71.1%: 12 patients relapsed within the first 5 years of follow-up. The overall response rate and 5-year overall survival were better for patients with an International Prognostic Index (IPI) 1 at diagnosis than for those with IPI 2 and IPI 3 (P

High levels of serum β2-microglobulin have been associated with human immunodeficiency virus infection and β2-microglobulin has been used with other serological and immunological markers for monitoring disease progression. The usefulness of β2-microglobulin as a prognostic marker during human immunodeficiency virus infection has been demonstrated in homosexual men and hemophiliacs; few and contradictory data have been reported in intravenous drug users. We have evaluated a cohort of 160 intravenous drug users (81 seronegative and 79 seropositive for human immunodeficiency virus infection) with normal renal function to assess whether serum β2-microglobulin could be used as a serological marker for monitoring infection; 78 healthy subjects were used as controls. Of 79 seropositive drug users, 54 were asymptomatic or had persistent generalized lymphoadenopathy the remaining 25 had the acquired immunodeficiency syndrome. Seropositive patients were tested for CD4+ lymphocyte number, p24 antigen and anti-p24 antibodies. A significant statistical difference was found in mean serum β2-microglobulin levels between seronegative and seropositive drug users. Moreover, higher levels of β2-microglobulin were observed in acquired immunodeficiency syndrome patients compared with asymptomatic or patients with persistent lymphadenopathy. A significant relationship was also observed between increased concentration of β2-microglobulin and the serological and immunological markers which indicate human immunodeficiency virus disease progression.

Axillary dissection in patients with breast cancer is associated with significant morbidity. Because 85% of the patients with a cancer < or = 1 cm have negative axillary nodal status, axillary dissection in these patients is only a staging procedure. A study of the sentinel lymph node (SLN) biopsy has been developed to determine axillary nodal status by means of a minimally invasive procedure. The aim of our study was to estimate the degree of reliability for identifying the SLN using a vital dye or lymphoscintigraphy, or a combination of the two. From January 1999 to May 2000 a series of 60 patients with breast cancer were evaluated for enrollment in the study. For the mapping procedure, lymphoscintigraphy in combination with injection of vital blue dye was performed in 24 patients, and vital dye alone was utilized in 36. Complete axillary dissection was performed in all patients after SLN biopsy. The mapping procedure was possible in 59 cases (98.3%). The SLNs were positive in 19 patients (32.2%) and negative in 40; in 38 of the 40 patients all axillary nodes were negative. There was concordance in 57 of 59 cases (96.6%). The false-negative rate was 5% (2/40). The overall sensitivity of the SLN biopsy was 90.4% (19/21), with a negative predictive value of 95% (38/40). Our results indicate that SLN biopsy guided by a gamma probe in combination with vital dye can identify a negative axilla with high accuracy. We conclude that the use of both techniques produces an optimal result, as they are complementary.

Background It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Patients and methods Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. Results ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Conclusions Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients.

In order to correctly perform record linkage among databases and accurately determine outcome indicators using hospital discharge data and death records, the quality of data is fundamental. A deterministic record linkage method was use to link hospital discharge data with records from the Death Registry in the Puglia region (Italy) for the years 2001-2006. Thirty-five percent of hospital discharge records in which the recorded discharge modality was "death" were not in agreement with the corresponding death records. Furthermore, 40% of hospital discharge records where the date of death was the same as the date of discharge from hospital did not record "death" as the discharge modality.

Background If spatial representations of hospitalization rates are used, a problem of instability arises when they are calculated on small areas, owing to the small number of expected and observed cases. Aim of this study is to assess the effect of smoothing, based on the assumption that hospitalization rates, when calculated at the municipal level, may be influenced by both the neighboring municipalities and the health service organization, as well as by environmental risk factors associated with the disease under study. Methods To smooth rates we hypothesize that each municipality belongs to two independent hierarchical levels; at one of these levels subjects may belong to a plurality of superior hierarchical objects. Two different models, so-called Multilevel Multimembership Models, are fitted. In the first the structure of random effects was: the municipality heterogeneity, the spatial dependence of the municipalities and the local health service organization. In the second we replaced the local health service organization effect with the environmental risk effect for each municipality area. The models were applied to spatially represent the rates of hospitalization for lung cancer and chronic obstructive pulmonary disease, determined through the hospital discharge forms recorded in Apulia for the year 2006. Results The effect of smoothing was greater in smaller municipalities and in those with a more unstable Risk Adjusted Rate (RAR) due to the small number of cases and of population at risk. When a hierarchical level representing the ASL is inserted, the model fits the data better. Conclusion Maps of hospitalization rates for lung cancer and chronic obstructive pulmonary disease, shaded with the rates obtained at the end of the smoothing procedure, change the visual picture of the disease distribution over the whole territory, and if detected by the model, seem to express a geographical distribution pattern in specific areas of the region. In the case of lung cancer, the models show a clear difference between RAR and smoothed RAR. The inclusion of a random effect indicating the ASL contributed to improve the graphic representation of the results, whereas the environmental risk was not found to be a better hierarchical level than the municipality for fitting of the model.

To evaluate different methodologic approaches for HER-2/neu analysis, we performed Southern, Northern, Western blot and histochemical assay on 112 samples from 86 primary tumors and 26 synchronous axillary metastatic lymph nodes of patients affected by operable breast cancer. Simultaneous statistical analysis of data obtained with the four methods (31 samples) showed that Western blot detected a higher percentage of alterations than the other assays (Cochran and Victor tests, 0.01 < p < 0.05). The same result was emphasized by pair analysis (McNemar, p < 0.05), which evaluated the assay data two by two. Immunohistochemical evaluations were more in accord with immunoprecipitation data when performed on frozen or Bouin-fixed, paraffin-embedded tissues than on formalin-fixed, paraffin-embedded tissues.

Malignant mesotheliomas of the hernial sac are uncommon and only a few cases have been diagnosed incidentally during herniorrhaphy procedures. The prognosis is poor and patient management is difficult because current treatment modalities do little to prolong survival. Molecular markers could be useful to identify potential therapeutic targets. Using microarray-comparative genomic hybridization (aCGH), two cases of peritoneal mesothelioma that were found incidentally at the time of hernia repair, were investigated. A high number of genetic aberrations was detected in both cases. The gains were prevalent. The tumors showed identical lost regions at 2q13, 6q25.3, 6q26, 6q26-->q27, 9q31.1-->9q31.3, 10p15.3, 11q13.2, 13q14.2, 19q13.42-->q43, and gains at 1p36.33, 3q29, 5p15.33, 7p22.3, 10p15.1-->10p14, 11q13.2, 12q24.23, 12q24.33, 16p13.3, 17p13.3, 18p11.31, 19q13.43, 21q21.1-->q21.2, 22q11.1-->q11.22, Xp21.2, Xq28. Survival was longer in the patient with a lower total number of genetic defects. aCGH provides a high-resolution map of copy number changes that may be critical to mesothelioma progression.

To compare record linkage (RL) procedures adopted in several Italian settings and a standard probabilistic RL procedure for matching data from electronic health care databases.Two health care archives are matched: the hospital discharges (HD) archive and the population registry of four Italian areas. Exact deterministic, stepwise deterministic techniques and a standard probabilistic RL procedure are applied to match HD for acute myocardial infarction (AMI) and diabetes mellitus. Sensitivity and specificity for RL procedures are estimated after manual review. Age and gender standardized annual hospitalization rates for AMI and diabetes are computed using different RL procedures and compared.Municipalities of Pisa and Roma, and Regions of Puglia and Piemonte.Residents in the considered areas on 31 December 2003 and corresponding episodes of hospitalization in the same areas during 2004.Measures of accuracy of RL procedures to match health care administrative databases.Data quality varies among archives and affects the decision rule of the probabilistic procedure. A unique decision rule was therefore adopted by means of choosing a positive predictive value of at least 98% for all the considered areas. The number of matched pairs identified with the probabilistic procedure is on average more then 11% greater than the number identified with the deterministic procedure. Sensitivity of probabilistic RL is similar or greater than that of other procedures. Differences between annual standardized hospitalization rates computed with stepwise deterministic RL and the standard probabilistic RL procedure vary among areas.Exact deterministic RL works well when unique identifiers and high quality data are available. The probabilistic procedure here proposed works as well as semi-deterministic RL when the latter implements a quality control of data or a manual review of final results. Otherwise, deterministic or semi-deterministic procedures imply classification errors of unknown size and direction.

Background Different studies have shown that obstructive sleep apnoea syndrome (OSAS), frequently associated with hypertension, represents a harmful and independent risk for cardiovascular diseases. The aim of our study was to ascertain whether the occurrence of OSAS could worsen microcirculatory impairment in very mild hypertensives. Materials and methods One hundred untreated very mild hypertensives underwent polysomnography and subdivided into 32 non-OSAS, 33 mild OSAS and 35 severe OSAS patients on standardized criteria. They underwent routine blood chemistry, ambulatory blood pressure monitoring and anthropometric analysis. Skin capillary density (n mm−2) of forearm (FAC) and periungueal (PUC) fields was obtained through videocapillaroscopy. By a venous congestion manoeuvre, PUC was maximized (CVC) and secondary capillary recruitment (GAIN) was calculated. These measurements served as indices of structural and functional capillary rarefaction, respectively. Results Severe OSAS hypertensives showed reduced FAC (P

Serum levels of angiogenic cytokines decrease after radiotherapy in patients with cancer, and this may be relevant for treatment response and progression-free survival. Herein, we set out to determine whether circulating fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and platelet-derived growth factor-beta (PDGF-beta) decrease after radiotherapy in patients with non-Hodgkin lymphomas (NHLs) and if so, whether their decrease correlates with age, tumour histotype and stage, and radiation dose.The serum levels of FGF-2, VEGF, HGF and PDGF-beta were evaluated before and after radiotherapy by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with age, histotype, stage and radiation dose.After radiotherapy, FGF-2, VEGF and PDGF-beta, but not HGF, significantly decreased in relation to the radiation dose and response. No correlation was established between cytokine levels, except for VEGF and PDGF-beta, which decreased in parallel. Haemoglobin levels did not decrease after radiotherapy, while FGF-2, VEGF, HGF and PDGF-beta levels did not correlate with age, NHL stage and histotype.Soluble FGF-2, VEGF and PDGF-beta levels decline after radiotherapy in NHLs, and may have predictive significance for response to treatment and recurrence.

Aim: To compare early hemorrhagic complications and the surgical and clinical outcome in the closure and non-closure of the parietal peritoneum in cesarean section (CS) patients. Material and Methods: We retrospectively evaluated 2,576 post-CS women subdivided and compared in two groups by open and closed parietal peritoneum (group I, n = 1,580, group II, n = 996). Results: The ultrasonographical detection of 23 blood collections (0.89%) was 14 in group I and 9 in group II, and of these we surgically treated 11 patients in group I and 8 patients in group II, with no statistical difference (p > 0.05); all group I patients showed hemoglobin point decreases and needed blood transfusions, with statistical significance (p < 0.05) linked to more severe early complications that make the post-CS outcome worse; no difference was confirmed in terms of antibiotic administration (p > 0.05). Conclusions: There was a significant increase of blood loss and transfusions in the first group. As the posterior surface of the Retzius space is open and if post-CS pathological bleeding occurs, blood can invade the peritoneal cavity causing a hemoperitoneum, with the possibility of hemorrhagic shock and a worse clinical outcome.