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Objectives: The aim of this study was to evaluate prenatal ultrasound features, fetal postnatal outcomes, and the need for postnatal surgery in the suspicion of ovarian torsion. Methods: We included patients with a singleton pregnancy with a suspicion of ovarian fetal cyst referred to our center. Data derived from prenatal ultrasound evaluations, delivery, and postnatal follow-up were then extracted from the hospital registers. Results: The ultrasound features of 32 fetal ovarian cysts and related neonatal outcomes were analyzed. The mean gestational age at diagnosis was 32 weeks (28-36), while the mean diameter of the cyst diagnosis was 34.8 ± 13.2 mm. In 78.1% of cases, the cysts did not change their characteristics during pregnancy, while in 9.4%, they increased their dimensions, and in 12.5%, they reduced their size. In 78.1% of cases, the diagnosis was confirmed postnatally, and in 40% of cases, a spontaneous regression occurred during follow-up. Surgery was performed in 60% of cases, and most of the time (66.7%), an adnexectomy was required. Conclusions: An unfavorable outcome was associated with cystic dimensions and ultrasound feature modifications during pregnancy. However, our study demonstrated that a hemorrhagic content is not always indicative of adnexal torsion, and spontaneous resolution may occur. In addition, only a few of the simple anechoic cysts managed surgically presented with necrosis at histopathological examination; therefore, a conservative approach might be proposed in those cases.

Objective: The anti-COVID vaccination campaign has led to a significant increase in the demand for allergology consultations in patients considered at risk of reaction to anti-COVID-19 vaccines. This study aims to describe the experience of the vaccination campaign held in Piedmont (Italy) which developed a new service of Allergy Call Center (ACC) thus providing for the screening and management of allergy high-risk patients during pandemic., Study Design: A retrospective analysis was performed on all patients considered at high risk for the development of allergic reactions who were referred by the Immunology and Allergy Unit of Azienda Ospedaliera Ordine Mauriziano in Turin, Italy, between December 2020 and December 2022 and also on ACC consultations., Methods: During the COVID-19 pandemic, Piedmont Region instituted the ACC, active from May 10th, 2021 to December 31st 2022, to allow vaccinating doctors to require a telephonic consultation for patients who were considered at high risk for the development of allergic reactions. If further diagnostic evaluations were required, the ACC scheduled a visit with a Consultant of the Unit to better assess the clinical situation of the patient. Furthermore, patients referred by General Practitioners, Occupational Doctors and other consultants were also evaluated by the Unit when required., Results: During the operational period the ACC received a total of 15,865 calls and referred only 336 patients to the unit (27.4% of the total referrals), while General Practitioners referred 499 patients (40.8%), Occupational Doctors referred 61 patients (4.9%), and other consultants referred 326 patients (26.6%)., Conclusions: Evaluation and management of a large volume of requests seemed to be facilitated by a proactive framework for screening patients at high risk for allergic reactions as the ones referred by our ACC. This approach led to a prominent decrease in allergological visits to our tertiary care Centre, reducing the waiting times and providing additional support for both patients and healthcare providers, thus allowing the vaccinations to be more easily handled., Competing Interests: Declarations. Conflict of interest: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royal-ties. Ethics Approval and Consent to Participate: The local Ethics Committee (Comitato Etico Territoriale interaziendale AOU Città della Salute e della Scienza di Torino) accepted the study, which was carried out in accordance with the Declaration of Helsinki’s principles., (© 2024. The Author(s).)

Background: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent., Methodology/principal Findings: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR., Conclusions/significance: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Grayscale abdomen ultrasound (US) is routinely performed in pregnant women with suspected pregnancy-related liver dysfunction, but its diagnostic yield is very low. We aimed to investigate the association between Doppler-US findings, liver stiffness measurement (LSM) and different causes of pregnancy-related liver dysfunction. This is a prospective cohort study of pregnant women referred to our tertiary center for any suspected gastrointestinal disease between 2017 and 2019 and undergoing Doppler-US and liver elastography. Patients with previous liver disease were excluded from the analysis. For group comparisons of categorical and continuous variables, the chi-square test or Mann-Whitney test, and the McNemar test were used, as appropriate. A total of 112 patients were included in the final analysis, of whom 41 (36.6%) presented with suspected liver disease: 23 intrahepatic cholestasis of pregnancy (ICP), six with gestational hypertensive disorders and 12 cases with undetermined causes of elevated liver enzymes. Values of LSM were higher and significantly associated with a diagnosis of gestational hypertensive disorder (AUROC = 0.815). No significant differences at Doppler-US or LSM were found between ICP patients and controls. Patients with undetermined causes of hypertransaminasemia showed higher hepatic and splenic resistive indexes than controls, suggesting splanchnic congestion. The evaluation of Doppler-US and liver elastography is clinically useful in patients with suspected liver dysfunction during pregnancy. Liver stiffness represents a promising non-invasive tool for the assessment of patients with gestational hypertensive disorders.

Introduction: Asthma, along with inhaled steroids, was initially considered a risk factor for worse clinical outcomes in COVID-19. This was related to the higher morbidity observed in asthma patients during previous viral outbreaks. This retrospective study aimed at evaluating the prevalence of asthma among patients admitted due to SARS-CoV-2 infection as well as the impact of inhaled therapies on their outcomes. Furthermore, a comparison between patients with asthma, COPD and the general population was made. Methods: All COVID-19 inpatients were recruited between February and July 2020 from four large hospitals in Northwest Italy. Data concerning medical history, the Charlson Comorbidity Index (CCI) and the hospital stay, including length, drugs and COVID-19 complications (respiratory failure, lung involvement, and the need for respiratory support) were collected, as well as the type of discharge. Results: patients with asthma required high-flow oxygen therapy (33.3 vs. 14.3%, p = 0.001) and invasive mechanical ventilation (17.9 vs. 9.5%, p = 0.048) more frequently when compared to the general population, but no other difference was observed. Moreover, asthma patients were generally younger than patients with COPD (59.2 vs. 76.8 years, p < 0.001), they showed both a lower mortality rate (15.4 vs. 39.4%, p < 0.001) and a lower CCI (3.4 vs. 6.2, p < 0.001). Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024). Discussion: Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay. In addition, the comparison of asthma with COPD patients confirmed the greater frailty of the latter, according to their multiple comorbidities.

The host range of bacteriophages defines their impact on bacterial communities and genome diversity. Here, we characterize 94 novel staphylococcal phages from wastewater and establish their host range on a diversified panel of 117 staphylococci from 29 species. Using this high-resolution phage-bacteria interaction matrix, we unveil a multi-species host range as a dominant trait of the isolated staphylococcal phages. Phage genome sequencing shows this pattern to prevail irrespective of taxonomy. Network analysis between phage-infected bacteria reveals that hosts from multiple species, ecosystems, and drug-resistance phenotypes share numerous phages. Lastly, we show that phages throughout this network can package foreign genetic material enclosing an antibiotic resistance marker at various frequencies. Our findings indicate a weak host specialism of the tested phages, and therefore their potential to promote horizontal gene transfer in this environment., (© 2021. The Author(s).)

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease that has rapidly spread to become a global pandemic. Bronchoscopy is clearly a high-risk manoeuvrer, so to continue endoscopic activity safely it was necessary to make many changes. We created different ways to access and exit the endoscopy theatre and reinforced our dressing/undressing regimens as well as equipment cleaning techniques. To prevent aerosol dispersion we used a bag valve mask with an antibacterial-antiviral filter, introducing the flexible bronchoscope orally rather than through the nose. For procedures with increased contagious risk a nasopharyngeal swab was required. From the date of the first case of COVID-19 in our hospital to December 31 2020, we performed 1027 bronchoscopies, in both negative and positive patients. No outbreaks occurred within the staff and no patients are known to have developed COVID-19 after a procedure. Our experience underscores how it is possible to continue endoscopic activity safely., (Copyright © 2021 SPLF and Elsevier Masson SAS. All rights reserved.)

Objectives: The aim of this study was to evaluate the obstetrical ultrasound simulator as an initiation tool for teaching obstetrical ultrasound scanning for beginners., Methods: Twenty medical students with no experience in ultrasound scan (US) received a basic theoretical ultrasonography course on US principles and 2nd trimester biometrical measurements. The participants were then divided into 2 groups (A, B). Only group A received a practical 2nd trimester scan training session on the simulator where they were asked to determine fetal and placental position, and to take the 3 biometrical standardized measurements. Group B had the same training session but with a real ultrasound machine and a pregnant volunteer. The 2 groups were then asked to perform an US session on real patients (22 weeks) during which they had to do the same US study. The time needed to complete the whole scan was analyzed. The quality of the measurements was compared based on the previously published Objective Quality Criteria scoring., Results: The mean total score was significantly (P=0.001) better for group A (14.3±1.4) compared to group B 10.3 (±2.75) for group A and B respectively. The time needed to accomplish the whole exam tended to be longer for group A (569±174s) compared to group A (479±104s) (P=0.18)., Conclusions: The simulator might be a useful initiation tool to obstetric ultrasound for those who never practiced. It might prove a time sparing procedure in the training process and allow trainees to reach a basic practice level before performing examinations on actual patients., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Evaluation of trainee's ability in obstetrical ultrasound is a time-consuming process, which requires involving patients as volunteers. With the use of obstetrical ultrasound simulators, virtual reality could help in assessing competency and evaluating trainees in this field., Objective: The objective of the study was to test the validity of an obstetrical ultrasound simulator as a tool for evaluating trainees following structured training by comparing scores obtained on obstetrical ultrasound simulator with those obtained on volunteers and by assessing correlations between scores of images and of dexterity given by 2 blinded examiners., Study Design: Trainees, taking the 2013 French national examination for the practice of obstetrical ultrasound were asked to obtain standardized ultrasound planes both on volunteer pregnant women and on an obstetrical ultrasound simulator. These planes included measurements of biparietal diameter, abdominal circumference, and femur length as well as reference planes for cardiac 4-chamber and outflow tracts, kidneys, stomach/diaphragm, spine, and face. Images were stored and evaluated subsequently by 2 national examiners who scored each picture according to previously established quality criteria. Dexterity was also evaluated and subjectively scored between 0 and 10. The Raghunathan's modification of Pearson, Filon's z, Spearman's rank correlation, and analysis of variance tests were used to assess correlations between the scores by the 2 examiners and scores of dexterity and also to compare the final scores between the 2 different methods., Results: We evaluated 29 trainees. The mean dexterity scores in simulation (6.5 ± 2.0) and real examination (5.9 ± 2.3) were comparable (P = .31). Scores with an obstetrical ultrasound simulator were significantly higher than those obtained on volunteers (P = .027). Nevertheless, there was a good correlation between the scores of the 2 examiners judging on simulation (R = 0.888) and on volunteers (R = 0.873) (P = .81)., Conclusion: An obstetrical ultrasound simulator is as good a method as volunteer-based examination for evaluating practical skills in trainees following structured training in obstetrical ultrasound. The threshold for success/failure should, however, be adapted as candidates obtain higher scores on the simulator. Advantages of the obstetrical ultrasound simulator include the absence of location and time constraints without the need to involve volunteers or to interfere with the running of ultrasound clinics. However, an obstetrical ultrasound simulator still lacks the ability to evaluate the trainees' ability to interact with patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this study, dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) was used to quantify the cerebral blood flow (CBF), the cerebral blood volume (CBV), and the mean transit time (MTT) and to analyze the changes in cerebral perfusion associated with the cortical lesions in 44 patients with relapsing-remitting multiple sclerosis. The cortical lesions showed a statistically significant reduction in CBF and CBV compared with the normal-appearing gray matter, whereas there were no significant changes in the MTT. The reduced perfusion suggests a reduction of metabolism because of the loss of cortical neurons. A small population of outliers showing an increased CBF and/or CBV has also been detected. The presence of hyperperfused outliers may imply that perfusion could evolve during inflammation. These findings show that perfusion is altered in cortical lesions and that DSC-MRI can be a useful tool to investigate more deeply the evolution of cortical lesions in multiple sclerosis.

Cortical inflammatory lesions have been correlated with disability and cortical atrophy in multiple sclerosis. The extent to which cortical lesion load is associated with longer-term physical and cognitive disability in different multiple sclerosis phenotypes has not yet been investigated. Thus, a 5-year prospective longitudinal study was carried on in a large group of patients with multiple sclerosis. Three hundred and twelve consecutive patients suffering from multiple sclerosis (157 relapsing remitting, 35 paediatric, 45 benign, 44 primary progressive and 31 secondary progressive) were enrolled in a 5-year prospective clinical and neuroimaging study. Several magnetic resonance parameters (including cortical lesion number and volume, contrast-enhancing cortical lesions and grey matter atrophy) were analysed to find associations with clinical and cognitive outcomes. Patients with high cortical lesion load had higher Expanded Disability Status Scale increase (median = 1.5; range = 0-3) during the study than both patients with low cortical lesion load (median = 1.0; range = 1-3, P < 0.001) and without cortical lesions (median = 0.5; range = -1 to 2, P < 0.001). Compared with clinically stable patients, 101 (32.4%) patients showing clinical progression at 5 years had the highest rate of cortical lesion accumulation (P < 0.001). Stepwise regression analysis revealed significant and independent contributions from age (β = 0.55), cortical lesion volume (β = 0.58), T(2) white matter lesion volume (β = 0.34) and grey matter fraction (β = 0.42) as predictors (final model with r(2 )= 0.657, P < 0.001) of Expanded Disability Status Scale change. Disease duration (β = 0.52, P < 0.001), cortical lesion volume (β = 0.67, P < 0.001), grey matter fraction (β = 0.56, P < 0.001) and T(2) white matter lesion volume (β = 0.31, P = 0.040) at baseline were found to be independent predictors of cognitive status at the end of the study. While confirming the relevance of cortical pathology in all multiple sclerosis phenotypes, but benign, our study suggests that grey matter and white matter changes in multiple sclerosis occur, at least, partly independently, and that grey matter, more than white matter, damage is associated with physical and cognitive disability progression. Thus, the combination of grey and white matter parameters gives a more comprehensive view of multiple sclerosis pathology and allows a better understanding of the progressive phase of the disease, which, however, seems more related to cortical damage than to subcortical white matter changes.

Objective: To measure the effects of disease-modifying drugs (DMDs) on the development of cortical lesions (CL) and cortical atrophy in patients with relapsing-remitting multiple sclerosis (RRMS)., Methods: RRMS patients (n = 165) were randomized to subcutaneous (sc) interferon (IFN) beta-1a (44 mcg three times weekly), intramuscular (im) IFN beta-1a (30 mcg weekly) or glatiramer acetate (GA; 20 mg daily). The reference population comprised 50 untreated patients. Clinical and MRI examinations were performed at baseline, 12 months and 24 months., Results: One hundred and forty-one treated patients completed the study. After 12 months, 37/50 (74%) of untreated patients developed ≥ 1 new CL (mean 1.6), compared with 30/47 (64%) of im IFN beta-1a-treated patients (mean 1.2, p = 0.021), 24/48 (50%) of GA-treated patients (mean 0.8, p = 0.001) and 12/46 (26%) of sc IFN beta-1a-treated patients (mean 0.4, p < 0.001). After 24 months, ≥ 1 new CL was observed in 41/50 (82%) of untreated (mean 3.0), 34/47 (72%) of im IFN beta-1a-treated (mean 1.6, p < 0.001), 30/48 (62%) of GA-treated (mean 1.3, p < 0.001) and 24/46 (52%) of sc IFN beta-1a-treated patients (mean 0.8, p < 0.001). Mean grey matter fraction decrease in DMD-treated patients at 24 months ranged from 0.7 to 0.8 versus 1.0 in untreated patients (p = 0.023)., Conclusions: Disease-modifying drugs significantly decreased new CL development and cortical atrophy progression compared with untreated patients, with faster and more pronounced effects seen with sc IFN beta-1a than with im IFN beta-1a or GA.

Background: The intrathecal production of immunoglobulin (Ig) is a major biological feature of multiple sclerosis (MS), and immunopathological studies have suggested a primary role of the humoral immune response in causing irreversible brain damage., Objective: To evaluate whether, in the early phases of MS, intrathecal Ig synthesis correlates with the presence of cortical lesions (CLs), and if their association could predict the clinical course of the disease., Methods: Eighty-six patients presenting with symptoms and signs suggestive of MS underwent a diagnostic work-up that included magnetic resonance imaging and cerebrospinal fluid examination. The risk ratios (RR) for conversion to MS and for a new disease activity were calculated., Results: Patients with clinically isolated syndromes (CIS) having CLs and intrathecal synthesis of Ig had the highest risk of conversion to MS (RR = 3.4; Wald 95% CI = 1.7-7.0, p < 0.001) whereas CIS patients without CLs and intrathecal synthesis of Ig had the lowest risk of conversion to MS (RR = 0.1, Wald 95% CI = 0.02-0.7, p < 0.001). The highest risk of having disease-related activity during the follow-up was observed in CIS and relapsing-remitting MS patients showing CLs and intrathecal Ig synthesis (RR = 2.1; Wald 95% CI = 1.5-3.1, p < 0.001) while the lowest in CIS and relapsing-remitting MS patients without CLs and intrathecal Ig synthesis (RR = 0.3; Wald 95% CI = 0.1-0.7, p < 0.001)., Conclusion: We observed that the association of intrathecal immunoglobulin synthesis and CLs was highly predictive of an earlier CIS conversion to MS as well as of a higher disease activity.

Background: Although gray matter (GM) atrophy is recognized as a common feature of multiple sclerosis (MS), conflicting results have been obtained in patients with clinically isolated syndromes (CIS). Methodologic and clinical constraints may take account for literature discrepancies., Methods: A total of 105 patients presenting with CIS and 42 normal controls (NC) were studied. At baseline, 65/105 patients with CIS met the criterion of dissemination in space of lesions (DIS+). All patients were clinically assessed by means of the Expanded Disability Status Scale every 6 months and underwent MRI evaluation at study entry and then annually for 4 years. Global and regional cortical thickness and deep GM atrophy were assessed using Freesurfer., Results: No significant reduction in GM atrophy was observed between the entire CIS group and the NC, excepting for the cerebellum cortical volume. When the 59 patients with CIS (46 DIS+, 13 DIS-) who converted to MS during the follow-up were compared to the NC, a significant atrophy in the precentral gyrus, superior frontal gyrus, thalamus, and putamen was observed (p ranging from 0.05 to 0.001). The multivariate analysis identified the atrophy of superior frontal gyrus, thalamus, and cerebellum as independent predictors of conversion to MS. CIS with atrophy of such areas had a double risk of conversion compared to DIS+ (odds ratio 9.6 vs 5.0)., Conclusion: Selective GM atrophy is relevant in patients with CIS who convert early to MS. The inclusion of GM analysis in the MS diagnostic workup is worthy of further investigation.

Objectives: The aim of this study was the comparison of a new double-coated paclitaxel-eluting coronary stent with bare-metal stent (BMS) in patients undergoing percutaneous coronary intervention., Background: Stent coating with biodegradable polymers as a platform for elution of drugs has the potential for complete elution of drugs and for decreasing the risk of late complications., Methods: Multicenter randomized trial comparing a paclitaxel-eluting stent (PES) coated with a biodegradable polymer and glycocalyx with the equivalent BMS. We randomly assigned 422 patients with de novo coronary lesions to PES (211 patients) or to BMS (211 patients). Primary end point was target vessel failure (TVF) defined as cardiac death, myocardial infarction, and target vessel revascularization. Clinical secondary end points were target vessel revascularization, target lesion revascularization, stent thrombosis (ST), and major adverse cardiovascular events (MACE). Angiographic secondary end points were late loss and binary restenosis., Results: At 1 year of follow-up, TVF rate was 9.5% in the PES group and 17.1% in the BMS group (P=0.02), and MACE rate was 10% in PES and 19% in BMS arm (P=0.009). All other secondary end points were reached but ST. ST rate was low and similar in both study arms., Conclusions: The study shows that patients treated with PES with dual coating technology had significantly lower incidence of TVF and MACE than those treated with BMS design; however, longer follow-up should be necessary to assess true advantages of this technology compared with the previous one., (Copyright © 2010 Wiley-Liss, Inc.)

Background: The presence of cortical lesions (CLs) and their topographic distribution in the brains of patients with multiple sclerosis (MS) have been clearly shown by recent histopathologic studies. CLs can also be assessed in vivo, with less sensitivity, by using specific MRI sequences. MRI-based lesion probability maps (LPMs) may partially overcome this lack of sensitivity and provide unique information on the spatial distribution and frequency of CLs in MS., Methods: A total of 149 patients with MS (103 relapsing-remitting [RR] and 46 primary progressive [PP]) underwent an MRI examination, which included the double inversion recovery (DIR) sequence for CL assessment. CL masks were then obtained for each patient and a cortical LPM (cLPM) was created for each MS subtype., Results: CLs were mainly distributed in the frontal (RR = 51.8%; PP = 50.5%) and temporal (RR = 30.4%; PP = 35.5%) lobes, with a prominent involvement of the motor (RR = 37.8%; PP = 30.6%) and anterior cingulate (RR = 9.2%; PP = 10.6%) cortices. The extent of brain lobe affected by CLs was higher in RR than in PP patients. The frequency of CL occurrence was higher in PP than in RR patients. Both measurements, however, did not show differences between the 2 MS subtypes at voxel-wise analysis., Conclusions: Patients with RRMS and PPMS share more similarities than differences in terms of CL number, volume, topographic distribution, and frequency. The similarities between histopathologic data and the findings reported here suggest that DIR images can accurately illustrate the focal pathology occurring in the cortical regions of patients with MS, providing clinically relevant information.

Background: Fatigue is one of the most frequent symptoms suffered by patients affected by multiple sclerosis. The patho-physiological basis of multiple sclerosis-related fatigue remains to be elucidated., Objective: Our aim was to investigate whether a particular pattern of deep and/or cortical grey matter atrophy is associated with fatigue in patients with multiple sclerosis., Methods: A total of 152 patients with relapsing-remitting multiple sclerosis were evaluated with the Expanded Disability Status Scale, the Fatigue Severity Status Scale (FSS), the Modified Fatigue Impact Scale and the Beck Depression Inventory. The thalamic and basal ganglia volume and the regional cortical thickness were analysed by means of FreeSurfer., Results: Based on Fatigue Severity Status Scale score, patients were divided into fatigued (FSS ≥ 4, 71 patients, 46.6%) and non-fatigued (FSS < 4, 81 patients, 53.4%). A significant atrophy of striatum, thalamus, superior frontal gyrus and inferior parietal gyrus was observed in fatigued patients compared with non-fatigued patients. The cognitive domain of Modified Fatigue Impact Scale significantly correlated with the volume of the striatum and with the cortical thickness of the posterior parietal cortex and middle frontal gyrus (R = 0.51-0.61), while the physical domain of Modified Fatigue Impact Scale significantly correlated with striatum volume and superior frontal gyrus cortical thickness (R = 0.50-0.54)., Conclusions: The regional analysis of deep and cortical grey matter atrophy suggests an association between the neurodegenerative process taking place in the striatum-thalamus-frontal cortex pathway and the development of fatigue in relapsing-remitting multiple sclerosis. The inclusion of the posterior parietal cortex as one of the best predictors of the Modified Fatigue Impact Scale cognitive domain suggests the major role of the posterior attentional system in determining cognitive fatigue in relapsing-remitting multiple sclerosis.

Background: Although neuropathological observations suggest that cerebellar cortex is a major site of demyelination in multiple sclerosis (MS), only a few MRI studies on cerebellar cortical pathology in MS are available., Objective: To analyse cerebellar cortical volume (CCV) and leucocortical lesions (CL) in MS, and their impact on clinical disability., Methods: The authors studied 125 patients divided into 38 Clinical Isolated Syndrome (CIS), 35 relapsing remitting multiple sclerosis (RRMS), 27 secondary progressive multiple sclerosis (SPMS) and 25 primary progressive multiple sclerosis, and 32 normal controls (NC). CCV and cerebellar CL number and volume were evaluated by means of Freesurfer software and Double Inversion Recovery, respectively., Results: Compared with NC (mean 113.2 + or - 2.6 cm(3)), the CCV was significantly reduced in CIS (105.4 + or - 2.2 cm(3), p=0.018), RRMS (104.0 + or - 2.0 cm(3), p=0.012), SPMS (98.8 + or - 2.0 cm(3), p<0.001) and PPMS (100.6 + or - 2.2 cm(3), p<0.001), even after age, gender and mean cortical volume correction. CL were observed in all patient groups and were an independent predictor of CCV and cerebellar dysfunction., Discussion: The authors confirm that the cerebellar cortex is severely and early affected by MS pathology. The monitoring of cerebellar cortical atrophy and CL may help to understand the mechanism underlying disability progression in MS.

Background: Although cognitive dysfunction affects a relevant portion of patients with multiple sclerosis (MS), its pathologic substrate has not been clarified and it does not seem entirely explained by white matter changes., Methods: A total of 100 consecutive patients with relapsing remitting MS (RRMS) and 42 normal controls (NC) were enrolled in the study. Cognitive performance was assessed by Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB). Regional cortical thickness (CTh) was evaluated by Freesurfer., Results: Thirty-one patients with RRMS failed 1 or 2 tests of BRB and were considered to have a mild cognitive impairment (mCI-RRMS), while 8 patients failed at least 3 tests and were classified as markedly impaired (sCI-RRMS). The mean CTh of mCI-RRMS and sCI-RRMS group was significantly lower than in NC (p < 0.001) and cognitively normal patients with RRMS (CN-RRMS) (p < 0.001). The regional analysis revealed significant cortical thinning in frontal and temporal regions (frontotemporal thinning) of CN-RRMS compared to NC, while a widespread pattern of cortical thinning was observed in mCI-RRMS and in sCI-RRMS compared to both CN-RRMS and NC. A correlation was observed between cognitive score (CS) and the mean CTh (r = -0.69, p < 0.001) and between CS and CTh of almost all the cortical areas analyzed (r value between -0.20 and -0.65, p < 0.01). A correlation was found between T2-WM-LV and mean CTh (r = -0.31, p = 0.004) or CS (r = 0.21, p = 0.031). The multivariate analysis confirmed a widespread cortical thinning as the best predictor of cognitive impairment., Conclusions: A widespread pattern of cortical thinning characterizes patients with cognitive dysfunction, suggesting such dysfunction as expression of a more aggressive and widespread cortical pathology.

Background: Neuropsychological deficits in patients with multiple sclerosis (MS) have been shown to be associated with the major pathological substrates of the disease, ie, inflammatory demyelination and neurodegeneration. Double inversion recovery sequences allow cortical lesions (CLs) to be detected in the brain of patients with MS. Modern postprocessing techniques allow cortical atrophy to be assessed reliably., Objective: To investigate the contribution of cortical gray matter lesions and tissue loss to cognitive impairment in patients with relapsing-remitting MS., Design: Cross-sectional survey., Setting: Referral, hospital-based MS clinic. Patients Seventy patients with relapsing-remitting MS., Main Outcome Measures: Neuropsychological performance was tested using the Rao Brief Repeatable Battery of Neuropsychological Tests, version A. Patients who scored 2 SDs below the mean normative values on at least 1 test of the Rao Brief Repeatable Battery of Neuropsychological Tests, version A, were considered to be cognitively impaired. A composite cognitive score (the cognitive impairment index) was computed. T2 hyperintense white matter lesion volume, contrast-enhancing lesion number, CL number and volume, normalized brain volume, and normalized neocortical gray matter volume were also assessed., Results: Twenty-four patients with relapsing-remitting MS (34.3%) were classified as cognitively impaired. T2 hyperintense white matter lesion volume and contrast-enhancing lesion number were not different between cognitively impaired and cognitively unimpaired patients. Cognitively impaired patients had a higher CL number (P = .01) and volume (P < .001) and decreased normalized brain volume (P = .02) and normalized neocortical gray matter volume (P = .002) when compared with cognitively unimpaired patients. Multivariate analysis revealed that age (beta = 0.228; P = .02), CL volume (beta = 0.452; P < .001), and normalized neocortical gray matter volume (beta = 0.349; P < .001) were independent predictors of the cognitive impairment index (r(2) = 0.55; F = 23.903; P < .001)., Conclusion: The burden of CLs and tissue loss are among the major structural changes associated with cognitive impairment in relapsing-remitting MS.

Background: In primary progressive multiple sclerosis (PPMS), a discrepancy exists between the modest brain white matter (WM) lesion burden and the severity of neurologic disability. Double-inversion recovery (DIR) sequences have improved MRI sensitivity in the detection of cortical lesions (CLs) in patients with relapsing-onset MS., Objective: This 2-year longitudinal study was designed to assess the frequency, extent, and rate of formation of CLs in PPMS and their relationship with T2 lesion volume (LV), gray matter (GM) atrophy, and disability., Methods: Forty-eight patients with PPMS underwent clinical and magnetic resonance examinations at baseline and after 2 years. The number and volume of CLs, WM T2 LV, and GM fraction (GMf) were assessed at baseline and at follow-up., Results: At baseline, CLs were detected in 81.2% of patients with PPMS. At least one new CL was found in 28 patients during the follow-up. In patients with PPMS, CL and T2 WM LVs increased over the follow-up. At baseline, CL number and volumes were significantly correlated with T2 WM LV, GMf, disease duration, and Expanded Disability Status Scale score, as well as with increasing GM atrophy and disability during the follow-up. A multivariate analysis showed that CL volume at baseline was an independent predictor of percentage GM volume change and disability accumulation during the subsequent 2-year period., Conclusions: Cortical lesions are a frequent finding in primary progressive multiple sclerosis. The extent of such abnormalities is associated with the extent of cortical atrophy and clinical disability, and is able to predict their changes over a medium time period.

Background: Using double inversion recovery (DIR) MRI, cortical lesions can be seen in the brain of patients with multiple sclerosis (MS). The burden of such lesions seems to be well correlated with the severity of MS-related disability., Objective: To investigate whether the extent of cortical damage in patients with benign MS (BMS) might contribute to explain their favorable clinical status., Methods: Forty-eight patients with BMS (Expanded Disability Status Scale [EDSS] score < or =3.0 and disease duration > or =15 years) and 96 patients with non-disabling, early relapsing-remitting (RR) MS (EDSS score < or =3.0 and disease duration < or =5 years) were studied. Brain MRI, including a DIR and a fluid-attenuated inversion recovery (FLAIR) sequence, was acquired at baseline and after 12 months. On DIR images, intracortical (ICL) and cortical-subcortical lesions (CSL) were identified and their number and volume calculated. Total white matter (WM) lesion volume was quantified on FLAIR images., Results: Compared with early RRMS, patients with BMS had lower number of ICL at both study time points (P < or = 0.001 for both comparisons). At one-year follow-up, a significant increase of ICL and CSL number and total volume was observed only in early patients with RRMS. The number and volume of cortical lesions was not correlated with WM lesion volume. Total ICL number at baseline, total cortical lesion volume at baseline, and total cortical lesion volume change were independent predictors of MS phenotype., Conclusion: In patients with BMS, the selective sparing of the cortex from disease-related focal pathology might be one of the factors associated to their favorable clinical status, independently of the (possible) accrual of WM lesions.

Cortical lesions (CLs) can be detected in the majority of patients with established multiple sclerosis (MS), but little is known about their evolution over time. This study was performed to investigate the short-term MRI evolution of CLs, with the ultimate aim to achieve a better in vivo understanding of their nature. Seven hundred and sixty-eight CLs from 107 MS patients (76 with relapsing-remitting [RR] and 31 with secondary progressive [SP] MS) were followed with brain MR examinations, including a double inversion recovery (DIR) sequence, every 6 months for 1 year. CLs' number, volume and morphological features were assessed at each time-point. Six hundred and eighty CLs (88.5%) remained morphologically unchanged during the follow-up period, while 74 (9.6%) showed an increase in size. Only 6 (0.8%) CLs seen at baseline (all in RRMS patients) disappeared at follow-up MRI scans. No enlarging CLs spread into the subcortical white matter. No CLs ever showed gadolinium enhancement. At baseline, the mean number of CLs was higher in SPMS than in RRMS patients (p<0.001), whereas the mean number of new CLs per patient after 1 year did not differ between the two groups. Over a one-year period, CLs can increase their number and size in a relevant proportion of MS patients, without spreading into the subcortical white matter or showing inflammatory features similar to those of white matter lesions. The short-term rate of CLs accumulation does not seem to vary according to the clinical stage of MS.

Introduction: Epilepsy is three to six times more frequent in MS than in the general population. Previous studies based on conventional magnetic resonance (MR) imaging have suggested a possible correlation between cortical inflammatory pathology and epileptic seizures. However, pure intracortical lesions (ICLs) are unlikely to be demonstrated with conventional MR. We applied the double inversion recovery (DIR) sequence in relapsing remitting MS (RRMS) patients with or without epileptic seizures in order to clarify the relationship between ICLs and epilepsy in MS in vivo., Methods: Twenty RRMS patients who had epileptic seizures (RRMS/E) during the course of the disease were studied for the presence of ICLs. A group of 80 RRMS patients with no history of seizures and matched for gender, age, disease duration, Expanded Disability Status Scale (EDSS) grading, and T2 lesion volume (T2-WMLV) was selected as reference population. ICLs were detected by applying the DIR sequence., Results: ICLs were observed in 18/20 (90%) RRMS/E and in 39/80 (48%) RRMS (p = 0.001). RRMS/E showed five times more ICLs (7.2 +/- 8.4) than RRMS (1.5 +/- 2.4; p = 0.015). The total ICLs volume was 6 times larger in RRMS/E than in RRMS (1.2 +/- 1.7 cm3 versus 0.2 +/- 0.2 cm3, p = 0.016). No significant difference was observed between RRMS and RRMS/E with regard to the number and volume of juxtacortical lesions and T2-WMLV., Discussion: Our findings indicate that RRMS/E have more extensive cortical inflammation than RRMS patients with no history of epilepsy. Inflammatory ICLs may be responsible for epilepsy in MS.

Background: A significant inflammatory pathologic disorder in the cortex of patients with multiple sclerosis (MS) has been demonstrated by ex vivo studies., Objective: To determine the frequency, time of appearance, and clinical relevance of intracortical lesions (ICLs) in MS in vivo., Design: Double inversion recovery sequence study., Setting: Multiple Sclerosis Centre of the Veneto Region. Patients We enrolled 380 patients (116 with clinically isolated syndrome [CIS], 163 with relapsing-remitting MS [RRMS], and 101 with secondary progressive MS [SPMS]) and 40 age- and sex-matched healthy volunteers between May 1, 2005, and December 31, 2006., Main Outcome Measures: We assessed the frequency and number of ICLs and brain parenchyma fraction, white matter T2 lesion volume, and clinical disability., Results: Although never observed in healthy volunteers, ICLs were detected in 58% of patients (36% of patients with CIS, 64% of patients with RRMS, and 73% of patients with SPMS). The number of ICLs was higher in patients with SPMS than in those with CIS or RRMS (P <.001), and patients with ICLs had a higher Expanded Disability Status Scale score (P = .004), a higher white matter T2 lesion volume (P = .008), a lower brain parenchyma fraction (P = .009), and a higher frequency of IgG oligoclonal bands (IgGOBs) (P <.001) than patients without ICLs. Patients positive for IgGOBs had more ICLs than patients negative for IgGOBs (P = .02). The number of ICLs correlated with the Expanded Disability Status Scale score (r = 0.48, P <.001), white matter T2 lesion volume (r = 0.38, P = .001), and brain parenchyma fraction (r = -0.47, P = .001). A significant association between ICLs and male sex was observed., Conclusions: Although more frequent in patients with SPMS, ICLs were observed from the early disease stages. The ICLs were more frequently detected in patients with IgGOBs and were associated with a higher clinical disability score and male sex. The ICLs may help to define MS clinical heterogeneity and prognosis in clinical settings.

Introduction: Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated., Methods: 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed., Results: We found a significant global cortical thinning in p-MS (2.22 +/- 0.09 mm), RR-MS (2.16 +/- 0.10 mm) and SP-MS (1.98 +/- 0.11 mm) compared to CIS (2.51 +/- 0.11 mm) and HV (2.48 +/- 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = -0.393, p = 0.03) and absent in p-MS (r = -0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas., Discussion: Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.

The optimal duration of treatment with clopidogrel after percutaneous coronary intervention (PCI) with stent placement remains controversial. The Randomized Argentine Clopidogrel Stent (RACS) trial was a prospective, randomized, nonblinded study of 1,004 patients undergoing PCI who were randomized after successful bare metal stent placement to 30 versus 180 days of clopidogrel; all patients also received aspirin. Patients were eligible regardless of whether they had presented with ST-elevation myocardial infarction (MI), acute coronary syndrome, or stable angina. The primary end point was a composite of death, MI, and stroke at 180 days. Baseline clinical characteristics showed no differences between groups in terms of age, gender, history, risk factors, or incidence of diabetes; 72% presented with an acute coronary syndrome and 15% had MI as the indication for PCI. At hospital discharge and 30 days, when the 2 groups received the same treatment, there were no significant differences between groups in frequency of death, MI, or stroke. However, from 30 days to 6 months, patients assigned to 6 months of clopidogrel reached the primary end point of death, MI, and stroke less frequently (4.99% vs 1.74%, p = 0.010, relative risk decrease 65%). No significant between-group differences were found in frequency of total bleeding (0.64% vs 1.52%, p = 0.34) for the control and study groups. In conclusion, after successful placement of a bare metal stent in a coronary artery, patients treated with 6 months of clopidogrel showed a trend toward fewer adverse events compared with those treated for 30 days.

Objective: To identify a bicycle saddle model for cyclists who cover long distances, to minimally reduce the compression on the structures of the pelvic floor, thereby protecting blood perfusion of the penis and avoiding possible consequences on penile erection., Materials and Methods: A comparison between a new geometric development of a bicycle saddle model (SMP) and one of the more frequently used models by professional cyclists was made. The measurement of the partial pressure of penile transcutaneous oxygen (PtcO(2)) in 29 healthy voluntary cyclists was recorded to investigate the differences of compression from two different saddles on the vascular structures of the perineum. The PtcO(2) was recorded at 3 and 10 minutes in conditions of static sitting. Then, the values of PtcO(2) were recorded for 15 minutes while the cyclists were in a 60-degree position and in stable hemodynamic conditions., Results: A t-test was performed to measure the level of confidence. The clear superiority of the SMP saddle in preventing vascular compression of the perineal structures was demonstrated to be statistically significant., Conclusion: The experiment validated the effectiveness of the SMP saddle in limiting the compression on the pelvic floor. In addition, the SMP saddle introduces compatible seat dimensions that cyclists prefer to cover long distances.

Percutaneous coronary interventions (PCIs) in diabetic patients with small reference diameter vessels remain an important challenge in interventional cardiology because it is associated with increased complications and restenosis rates. Plain old balloon angioplasty (POBA) has limited efficacy in patients with lesions in small vessels. Although coronary stenting (stent) has been demonstrated to improve both immediate and long-term results after coronary intervention, small reference diameter is a strong predictor of restenosis after stent implantation. Thus, the question of how to best treat diabetic patients with lesions in small reference diameter remains unanswered. The purpose of this international and multicenter study was to compare the incidence of angiographic restenosis between percutaneous transluminal coronary angioplasty (PTCA) and stent in diabetic patients undergoing PCI of small reference diameter vessels using a specially designed phosphoryl choline (PC)-coated stent for small vessels. The patient population comprised of 220 diabetic patients with lesions in small reference diameter (< 2.9 mm but > 2.0 mm) that were randomized into two different PCI strategies: PTCA with provisional stenting (n = 109) versus stent (n = 111). In the PTCA arm, 26 patients (24%) crossed over to stent during the initial procedure; glycoproteins IIb to IIIa was used in 40.5% of patients in both groups. During initial procedure and at 30 days, both strategies of revascularitation had similar clinical success and acute complications. During long-term follow-up, even though requirements of target vessel revascularization and incidence of major adverse cardiovascular event were similar with both techniques, angiographic binary restenosis (45% with PTCA and 28% with stents, P = .047), net gain (0.74 mm with POBA and 0.94 mm with stents, P = .008), and freedom from target vessel failure (66% with POBA and 81.2% with stents, P = .013) were significantly improved when diabetic patients were initially treated with stent therapy. In summary, in diabetic patients with small coronary arteries, the use of a coronary PC coated stent as a primary device during percutaneous interventions was associated with better angiographic and long-term outcome.

Purpose: To compare percutaneous coronary intervention (PCI) using stent implantation versus coronary artery bypass graft (CABG) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery (LAD)., Methods: 230 patients with multiple vessel disease and severe stenosis of the proximal LAD (113 with PCI, 117 with CABG). They were a cohort of patients from the randomised ERACI (Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease) II study., Results: Both groups had similar baseline characteristics. There were no significant differences in 30 day major adverse cardiac events (death, myocardial infarction, stroke, and repeat procedures) between the strategies (PCI 2.7% v CABG 7.6%, p = 0.18). There were no significant differences in survival (PCI 96.4% v CABG 95%, p = 0.98) and survival with freedom from myocardial infarction (PCI 92% v CABG 89%, p = 0.94) at 41.5 (6) months' follow up. However, freedom from new revascularisation procedures (CABG 96.6% v PCI 73%, p = 0.0002) and frequency of angina (CABG 9.4% v PCI 22%, p = 0.025) were superior in the CABG group., Conclusion: Patients with multivessel disease and significant disease of the proximal LAD randomly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infarction at long term follow up. Repeat revascularisation procedures were higher in the PCI group.

Objective: The purpose of this study was to compare percutaneous transluminal coronary revascularization (PTCR) employing stent implantation to conventional coronary artery bypass graft surgery (CABG) in symptomatic patients with multivessel coronary artery disease., Background: Previous randomized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results. However, CABG was associated with significantly fewer repeat revascularization procedures., Methods: A total of 2,759 patients with coronary artery disease were screened at seven clinical sites, and 450 patients were randomly assigned to undergo either PTCR (225 patients) or CABG (225 patients). Only patients with multivessel disease and indication for revascularization were enrolled., Results: Both groups had similar clinical demographics: unstable angina in 92%; 38% were older than 65 years, and 23% had a history of peripheral vascular disease. During the first 30 days, PTCR patients had lower major adverse events (death, myocardial infarction, repeat revascularization procedures and stroke) compared with CABG patients (3.6% vs. 12.3%, p = 0.002). Death occurred in 0.9% of PTCR patients versus 5.7% in CABG patients, p < 0.013, and Q myocardial infarction (MI) occurred in 0.9% PTCR versus 5.7% of CABG patients, p < 0.013. At follow-up (mean 18.5 +/- 6.4 months), survival was 96.9% in PTCR versus 92.5% in CABG, p < 0.017. Freedom from MI was also better in PTCR compared to CABG patients (97.7% vs. 93.4%, p < 0.017). Requirements for new revascularization procedures were higher in PTCR than in CABG patients (16.8% vs. 4.8%, p < 0.002)., Conclusions: In this selected high-risk group of patients with multivessel disease, PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery. Repeat revascularization procedures were higher in the PTCR group.

Background: Lipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis, which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus., Methods and Results: A total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger in specimens from patients with diabetes (7+/-2%) than in specimens from patients without diabetes (2+/-1%; P:=0.01), and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22+/-3%) than in specimens from patients without diabetes (12+/-1%; P:=0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%; P:=0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet., Conclusions: Coronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus.

Objective: This study sought to compare two strategies of revascularization in patients obtaining a good immediate angiographic result after percutaneous transluminal coronary angioplasty (PTCA): elective stenting versus optimal PTCA. A good immediate angiographic result with provisional stenting was considered to occur only if early loss in minimal luminal diameter (MLD) was documented at 30 min post-PTCA angiography., Background: Coronary stenting reduces restenosis in lesions exhibiting early deterioration (>0.3 mm) in MLD within the first 24 hours (early loss) after successful PTCA. Lesions with no early loss after PTCA have a low restenosis rate., Methods: To compare angiographic restenosis and target vessel revascularization (TVR) of lesions treated with coronary stenting versus those treated with optimal PTCA, 116 patients were randomized to stent (n=57) or to optimal PTCA (n=59). After randomization in the PTCA group, 13.5% of the patients crossed over to stent due to early loss (provisional stenting)., Results: Baseline demographic and angiographic characteristics were similar in both groups of patients. At 7.6 months, 96.6% of the entire population had a follow-up angiographic study: 98.2% in the stent and 94.9% in the PTCA group. Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group (1.95 vs. 1.5 mm; p < 0.03). However, late loss was significantly higher in the stent than the PTCA group (0.63+/-0.59 vs. 0.26+/-0.44, respectively; p=0.01). Hence, net gain with both techniques was similar (1.32< or =0.3 vs. 1.24+/-0.29 mm for the stent and the PTCA groups, respectively; p=NS). Angiographic restenosis rate at follow-up (19.2% in stent vs. 16.4% in PTCA; p=NS) and TVR (17.5% in stent vs. 13.5% in PTCA; p=NS) were similar. Furthermore, event-free survival was 80.8% in the stent versus 83.1% in the PTCA group (p=NS). Overall costs (hospital and follow-up) were US $591,740 in the stent versus US $398,480 in the PTCA group (p < 0.02)., Conclusions: The strategy of PTCA with delay angiogram and provisional stent if early loss occurs had similar restenosis rate and TVR, but lower cost than primary stenting after PTCA.

Background: Early loss of minimal luminal diameter of >0.3 mm after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of restenosis. The underlying mechanism of this early loss is unknown and thrombus may be a contributing factor., Methods: We performed a prospective study using quantitative computerized planimetry on coronary tissue specimens obtained by directional coronary atherectomy of 24 lesions in which early loss occurred 22+/-9 minutes after successful PTCA., Results: Thrombus was present in 9 (37%) of 24 coronary specimens. Segmental areas (mm2) and percentage of total area were distributed as follows: sclerotic tissue, 4.07+/-0.7 mm2 (63%+/-6%); fibrocellular tissue, 0.97+/-0.27 mm2 (16%+/-4%); hypercellular tissue, 0.99+/-0.29 mm2 (12%+/-3%); atheromatous gruel, 0.18+/-0.07 mm2 (3%+/-0.1%); and thrombus, 0.24+/-0.15 mm2 (6%+/-0.4%). There was no difference in the relative early loss index between lesions with or without thrombus (35%+/-7% vs 26%+/-2%, respectively; P= .87). Multiple stepwise regression analysis did not identify any histologic predictors of relative early loss index., Conclusion: Histopathologic analysis of coronary lesions with early loss after successful PTCA suggests that thrombus may not play a significant role in this angiographic phenomenon.

The authors report the case of a patient affected by a cervical spine trauma who developed upper airway obstruction as a result of a retropharyngeal hematoma. An endotracheal intubation with a small-diameter tube was performed, but ventilation and oxygenation were not adequate. An early Percutaneous Dilational Tracheostomy with the Ciaglia technique was then performed. The risk of upper airway obstruction by retropharyngeal hematoma after cervical spine trauma is discussed in this article, as are the feasibility and benefits of using Percutaneous Dilational Tracheostomy in emergency cases of upper airway obstruction.

One hundred four patients presenting with acute myocardial infarction < 24 hours after onset were randomized to 2 groups: group I (n = 52) was treated with balloon angioplasty followed electively with Gianturco Roubin II stents, and group II was treated with conventional balloon angioplasty alone (n = 52). All lesions were suitable for stenting. Baseline clinical, demographic, and angiographic characteristics were similar in the 2 groups. Procedural success was defined as no laboratory death or emergent coronary bypass, Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow after the procedure in a culprit vessel, and a residual stenosis < or = 30% for coronary angioplasty and < 20% for stent. Procedural success was 98% in group I versus 94.2% in group II, p = NS. Thirteen patients in group II (25%) had bailout stenting during the initial procedure. Adverse in-hospital events including either death, nonelective coronary bypass, recurrent ischemia, and reinfarction occurred in 3.8% in group I versus 19.2% in group II, p = 0.03. Repeat angiography performed routinely before hospital discharge revealed TIMI 3 flow in the infarct-related artery in 98% in group I versus 83% in group II, p < 0.03. At late follow-up, event-free survival was significantly better in the stent (83%) than in the coronary angioplasty (65%) group (p = 0.002). The procedural in-hospital and late outcomes of this randomized study demonstrate that balloon angioplasty followed electively by coronary stents can be used as the primary modality for patients undergoing coronary interventions for acute myocardial infarction, increasing TIMI 3 flow, reducing in-hospital adverse events, and improving late outcome compared with balloon angioplasty alone.

Background: A number of treatments, including Nd-YAG laser therapy, brachytherapy, cryotherapy, electrocautery, and photodynamic therapy, can re-open the obstructed bronchial lumen in patients with inoperable obstructive bronchial tumours. None of these is considered to be a "gold standard"., Methods: The results of a retrospective study of 98 patients treated by radiofrequency tissue ablation and subsequent cryotherapy between January 1994 and June 1995 are reported. The patients were divided in two groups according to whether they were treated either after (group 1, n = 50) or before (group 2, n = 48) radiotherapy and/or chemotherapy. Bronchoscopic follow up was performed. The intervention was considered successful if the lumen was opened by > 80% and partially successful if it was opened by > 50%., Results: In group 1 treatment was successful in 60%, partially successful in 32%, and unsuccessful in 8%. The median survival time was five months from the time of bronchoscopic surgery. In group 2 treatment was successful in 66%, partially successful in 21.5%, and unsuccessful in 12.5%, with a median survival time of 14 months from the time of bronchoscopic treatment. Forty patients (24 in group 1 and 16 in group 2) received a Dumon stent., Conclusions: Radiofrequency bronchoscopic surgery with cryotherapy appears to be a useful technique in the treatment of tracheobronchial obstruction.

Background: Restenosis remains the major limitation of percutaneous coronary revascularization. Macrophages release cytokines, metalloproteinases, and growth factors that may induce smooth muscle cell migration and proliferation. We tested the hypothesis that primary lesions that develop restenosis after coronary atherectomy have more macrophages and smooth muscle cells than primary lesions that do not develop restenosis., Methods and Results: Fifty patients with unstable angina were identified. Total and segmental areas were quantified on trichrome-stained sections of coronary atherectomy tissue. Macrophages and smooth muscle cells were identified by immunohistochemical staining. Restenosis, defined as > 50% stenosis diameter by quantitative cineangiography, was present in 30 patients. The other 20 patients (< 50% stenosis) constitute the "no restenosis" group. The percentages of smooth muscle cell areas were similar in specimens from patients with and without restenosis (57 +/- 5% and 52 +/- 6%) (P = NS). However, macrophage-rich areas were larger in plaque tissue from patients with restenosis (20.4 +/- 2%) than in tissue from patients without restenosis (9.3 +/- 2%) (P = .0007). Multiple stepwise logistic regression analysis identified macrophages as the only independent predictor for restenosis (P = .006)., Conclusions: Macrophages are increased in coronary atherectomy tissue from primary lesions that develop restenosis, suggesting a possible role for macrophages in the restenotic process after percutaneous coronary intervention.

Background: Macrophage expression of tissue factor may be responsible for coronary thrombogenicity in patients with plaque rupture. In patients without plaque rupture, smooth muscle cells may be the thrombogenic substrate. This study was designed to identify the cellular correlations of tissue factor in patients with unstable angina., Methods and Results: Tissue from 50 coronary specimens (1560 pieces) from patients with unstable angina and 15 specimens from patients with stable angina were analyzed. Total and segmental areas (in square millimeters) were identified with trichrome staining. Macrophages, smooth muscle cells, and tissue factor were identified by immunostaining. Tissue factor content was larger in unstable angina (42 +/- 3%) than in stable angina (18 +/- 4%) (P = .0001). Macrophage content was also larger in unstable angina (16 +/- 2%) than in stable angina (5 +/- 2%) (P = .002). The percentage of tissue factor located in cellular areas was larger in coronary samples from patients with unstable angina (67 +/- 8%) than in samples from patients with stable angina (40 +/- 5%) (P = .00007). Multiple linear stepwise regression analysis showed that coronary tissue factor content correlated significantly (r = .83, P < .0001) with macrophage and smooth muscle cell areas only in tissue from patients with unstable angina, with a strong relationship between tissue factor content and macrophages in the atheromatous gruel (r = .98, P < .0001)., Conclusions: Tissue factor content is increased in unstable angina and correlates with areas of macrophages and smooth muscle cells, suggesting a cell-mediated thrombogenicity in patients with acute coronary syndromes.

Although coronary stenting has been useful in the treatment of patients with suboptimal results, abrupt closure, and threatening occlusion after percutaneous transluminal coronary angioplasty (PTCA), its use in patients with acute myocardial infarction (AMI) is controversial because of the presence of intracoronary thrombus. In this study intracoronary stenting was used to treat suboptimal results and complications in 30 patients (35 lesions) undergoing PTCA during AMI. There were 28 men and 2 women, mean age 58 +/- 12 years. Thirteen patients (43%) had undergone rescue PTCA because of unsuccessful thrombolysis. Four patients had Killip's grade IV, 5 Killip's grade III, and 21 Killip's grade < or = 2 heart failure. Stents were placed in the 35 lesions because of suboptimal result (n = 19), early loss (n = 9), abrupt closure (n = 2), and coronary dissection with threatening occlusion (n = 5). All stents were deployed successfully. In-hospital complications included 1 in-hospital death (3.0%); no patient required emergency coronary artery bypass graft surgery. One patient (3.0%) developed abrupt closure and was successfully treated with PTCA and intracoronary thrombolysis. Vascular complications requiring blood transfusion developed in 3 of 30 patients (10%). At 11.8 months (range 4 to 24) follow-up, there were no deaths or myocardial infarction. One patient underwent coronary artery bypass grafting. The remaining patients were free of angina at follow-up. Thus, intracoronary stents can be used successfully to treat both suboptimal results and complications occurring in patients undergoing PTCA during AMI.

Cryosurgery is one of the techniques available for bronchoscopic treatment of malignant and nonmalignant tracheobronchial stenosis; other techniques are electrosurgery, laser therapy, and endobronchial brachytherapy. Our experience began in 1976 and includes more than 300 patients treated with bronchoscopic cryosurgery either for malignant (the majority) or for nonmalignant tracheobronchial lesions. This study was performed on 234 patients treated in the years 1979 to 1988 subdivided as follows: 183 malignant tumors, 44 benign tumors, and 7 tumors of uncertain prognosis (adeno). The study demonstrated satisfying results in both (palliative in the first case, almost radical in the second one). The aim of our work was to report our personal data and to compare advantages and limits of this technique to others.

The study was conducted on patients with initially diagnosed tuberculosis encountered in 1986-87. A series of 269 bacterial antibiograms performed on sputum [correction of excreate] and other materials was examined in order to ascertain the resistance of Koch's bacillus to R/AMP, INH, SM and EMB. Primary drug resistance was found in 64 cases (23.79% of the total) and was isolated in 32 (11.89%), multiple in the rest. The response to the individual antibiotics was a follows resistance to INH was isolated in 11 cases (4.08%), combined with resistance to other drugs in 27 (10.03%); resistance to SM was isolated in 13 cases (4.81%) multiple in 24 (8.92%); resistance to R/AMP was isolated in 4 cases (1.48%), multiple in 14 (5.2%); resistance to EMB was isolated in 4 (1.48%) multiple in 19 (7.06%). Comparison with earlier studies in the Turin area highlights that the incidence of TB, in decline up to 1979, significantly increased in the period considered.

Six cases of scleroderma with pulmonary involvement, either isolated or accompanied by other visceral signs, observed between 1985 and 1987 have been examined. Patients were undergoing treatment with cortisone drugs in 4 cases and azathioprine in 2. Chest X-ray documented a picture of nodular opacities in 3 cases, reticular in 2 and miliariform in 1. B.A.L. revealed a picture of prevalently neutrophil alveolitis in all subjects, while transbronchial biopsy showed a finding of macrophagic infiltration in 2 cases, and one of fibroblastic proliferation in 4. The anatomoclinical damage was reflected adequately by spirometric tests and above all by the DLCO, while Gallium 67 scan and measurement of the A.C.E. were not very sensitive.