Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Review of general suggestions on physical activity to prevent and treat gestational and pre-existing diabetes during pregnancy and in postpartum.

The aim of this review is to provide general suggestions on physical activity (PA) in pre-gestational and gestational diabetes mellitus (GDM) and encourage women to take part in safe and effective activities throughout pregnancy, in the absence of other contraindications. PA before and during pregnancy and in postpartum has many positive effects on the mother, as it could reduce the risk of GDM, excessive weight gain and lower back pain and also prevents, in the postpartum, diabetes mellitus. It may also reduce the duration of labour and complications at childbirth, fatigue, stress, anxiety and depression, thereby leading to an improved sense of wellbeing. Clinically, it is thought to help prevent preeclampsia and premature birth even though RCTs provide conflicting evidence with regard to the prevention of GDM. The main reason for this rests on the fact that the majority of clinical trials have not been able to replicate the preventive effect of PA on the onset of GDM, such as the different adherence of the patient to PA. Herein, we survey the literature regarding exercise and PA on GDM prevention and treatment as well as on clinical outcomes in pre-GDM in pregnancy. On the basis of the current literature, we also present a series of general recommendations and suggestions on PA and exercise training in pregnancy among both diabetic patients and those at risk for GDM.

Hypertensive disorders during pregnancy and 3 years after delivery in women with gestational hyperglycemia.

AIMS: Women with gestational hyperglycemia commonly experience hypertensive disorders during pregnancy. More information is needed about how hypertension develops in these patients over time. We investigated the prevalence of hypertension during and 3 years after pregnancy in Caucasian women with gestational hyperglycemia. We also investigated metabolic syndrome presence, glucose tolerance status, insulin sensitivity and insulin secretion levels in the follow-up period. METHODS: In a prospective longitudinal study with a 3-year follow-up, we assessed hypertension status and clinical-related characteristics of 103 consecutive women with gestational hyperglycemia sub-grouped according to their hypertensive status during and after pregnancy. RESULTS: Overall, 29 (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4 chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a normotensive pregnancy). Women with hypertension after pregnancy had higher BMI, metabolic syndrome rate and worse insulin resistance indexes than normotensive women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo regular monitoring during and after pregnancy to detect metabolic and clinical impairments and to prevent cardiovascular harm.

Analysis of CT features and quantitative texture analysis in patients with lung adenocarcinoma: a correlation with EGFR mutations and survival rates.

AIM: To investigate the correlation between conventional computed tomography (CT) features, quantitative texture analysis (QTA), epidermal growth factor receptor (EGFR) mutations, and survival rates in patients with lung adenocarcinoma. MATERIALS AND METHODS: Sixty-eight patients were evaluated for conventional CT features and QTA in this retrospective study. A multiple logistic regression analysis and receiver operating characteristics (ROC) curve analysis versus death and EGFR status was performed for CT features and QTA in order to assess correlation between CT features, QTA, EGFR mutations, and survival rates. A p-value <0.05 was regarded to indicate a statistically significant association. RESULTS: An EGFR mutation was identified in 26/68 tumours (38.2%). A negative association was found between EGFR mutation and emphysema (p < 0.0001) whereas a positive correlation was found with necrosis (p=0.017), air bronchogram (p=0.0304), and locoregional infiltration (p=0.0018). Mean, standard deviation, and skewness were found to have significant correlation with EGFR mutation (p=0.0001; p=0.0001; p=0.0459; Fig 3). The only parameter correlated with the event death was entropy (r=0.2708; p=0.0329). CONCLUSION: Both qualitative and quantitative analysis disclosed potential associations between CT features and QTA parameters, EGFR mutations and prognosis; these correlations need to be confirmed in larger studies to be used as imaging biomarkers in the management of patients affected by lung adenocarcinoma.

Systematic review of high-intensity focused ultrasound ablation in the treatment of breast cancer.

BACKGROUND: A systematic review was undertaken to assess the clinical efficacy of non-invasive high-intensity focused ultrasound (HIFU) ablation in the treatment of breast cancer. METHODS: MEDLINE/PubMed library databases were used to identify all studies published up to December 2013 that evaluated the role of HIFU ablation in the treatment of breast cancer. Studies were eligible if they were performed on patients with breast cancer and objectively recorded at least one clinical outcome measure of response (imaging, histopathological or cosmetic) to HIFU treatment. RESULTS: Nine studies fulfilled the inclusion criteria. The absence of tumour or residual tumour after treatment was reported for 95·8 per cent of patients (160 of 167). No residual tumour was found in 46·2 per cent (55 of 119; range 17-100 per cent), less than 10 per cent residual tumour in 29·4 per cent (35 of 119; range 0-53 per cent), and between 10 and 90 per cent residual tumour in 22·7 per cent (27 of 119; range 0-60 per cent). The most common complication associated with HIFU ablation was pain (40·1 per cent) and less frequently oedema (16·8 per cent), skin burn (4·2 per cent) and pectoralis major injury (3·6 per cent). MRI showed an absence of contrast enhancement after treatment in 82 per cent of patients (31 of 38; range 50-100 per cent), indicative of coagulative necrosis. Correlation of contrast enhancement on pretreatment and post-treatment MRI successfully predicted the presence of residual disease. CONCLUSION: HIFU treatment can induce coagulative necrosis in breast cancers. Complete ablation has not been reported consistently on histopathology and no imaging modality has been able confidently to predict the percentage of complete ablation. Consistent tumour and margin necrosis with reliable follow-up imaging are required before HIFU ablation can be evaluated within large, prospective clinical trials.

Evaluation of image quality, radiation dose and diagnostic performance of dual-energy CT datasets in patients with hepatocellular carcinoma.

AIM: To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. MATERIAL AND METHODS: Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. RESULTS: Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets (p>0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p=0.001; mixed versus 140 kVp, p=0.001; 80 kVp versus mixed, p=0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets (p<0.001). CONCLUSIONS: The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

The contribution of histopathological examination to the diagnosis of cervico-facial actinomycosis: a retrospective analysis of 68 cases.

Cervico-facial actinomycosis is an infectious, suppurative, and granulomatous disease due to Actinomyces species. Usually, the diagnosis is confirmed by microbiological cultures; however, the need for careful anaerobic handling of specimens often makes it difficult to obtain an effective microbial growth. Therefore, we conducted a retrospective study on biopsy samples from patients with a clinical suspicion of cervico-facial actinomycosis, in order to determine whether accurate histopathological examination could reliably confirm the diagnosis. A retrospective revision of formalin-fixed, paraffin-embedded archival material from 68 cases of cervico-facial lesions, with negative culture for anaerobic/microaerophilic microorganisms, was performed. Twelve serial sections for each case were cut from the paraffin blocks, individually collected on positively charged slides to obtain good section-to-slide adhesion, and stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). Histopathological examination of the serial sections allowed the identification of bacterial colonies consistent with actinomycetes in 22 cases (32 %). The proposed histopathological examination allowed the retrospective diagnosis of cervical actinomycosis in one-third of clinical specimens that remained misdiagnosed following traditional H&E examination.

Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir.

A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated.

Phytoplankton spring bloom in the NW Mediterranean Sea under climate change.

The spring phytoplankton bloom is the main event influencing ecosystem richness in the pelagic realm of the Northwestern Mediterranean Sea (NW Med Sea). The Marine Strategy Framework Directive requires the achievement of a good ecological status for the pelagic habitat, and phytoplankton bloom phenology has been used as an indicator of the status of offshore waters. In this work we investigate interannual changes in the timing and magnitude of the phytoplankton bloom in the NW Med Sea, using phenological metrics. Daily maps of Chl-a concentration from 1998 to 2022 obtained by CMEMS were used to analyse bloom phenological metrics in 5 representative sites in the area. Chlorophyll-a data from 1998 to 2007 were used for determining the climatological behaviour, while 2008-2022 was identified as the study period. For this latter period, yearly spring bloom were identified and interannual variability and overall trends were analysed for each of the phenological metrics considered. Winter oceanographic and meteorological data were analysed to investigate possible correlations with the subsequent spring bloom. The frequency of anomalous years is increasing, both for bloom intensity and sea temperature. Bloom analysis revealed a negative trend only in some areas, but a steep decrease in the last 7 years was noticeable for all sites considered. Correlations of the Chl-a concentration during bloom with oceanographic variables revealed the importance of temperature, both marine and atmospheric, while Mixed Layer Depth played a lesser role. This work contributes to a better understanding of the dynamics of an area already under severe threat from human activities.

[MR-guided focused ultrasound. Current and future applications]. / MR-gesteuerter fokussierter Ultraschall. Aktuelle und potenzielle Indikationen.

STANDARD RADIOLOGICAL METHODS: High-intensity focused ultrasound (synonyms FUS and HIFU) under magnetic resonance imaging (MRI) guidance (synonyms MRgFUS and MR-HIFU) is a completely non-invasive technology for accurate thermal ablation of a target tissue while neighboring tissues and organs are preserved. METHODICAL INNOVATIONS: The combination of FUS with MRI for planning, (near) real-time monitoring and outcome assessment of treatment markedly enhances the safety of the procedure. ACHIEVEMENTS: The MRgFUS procedure is clinically established in particular for the treatment of symptomatic uterine fibroids, followed by palliative ablation of painful bone metastases. Furthermore, promising results have been shown for the treatment of adenomyosis, malignant tumors of the prostate, breast and liver and for various intracranial applications, such as thermal ablation of brain tumors, functional neurosurgery and transient disruption of the blood-brain barrier.

Diagnostic accuracy of colour Doppler ultrasonography, CT angiography and blood-pool-enhanced MR angiography in assessing carotid stenosis: a comparative study with DSA in 170 patients.

PURPOSE: This study was undertaken to prospectively evaluate the diagnostic performance of colour Doppler ultrasonography (CDUS), first-pass (FP) and steady-state (SS) contrast-enhanced magnetic resonance angiography (MRA) and computed tomography angiography (CTA) of the carotid arteries using digital subtraction angiography (DSA) as the reference standard. MATERIALS AND METHODS: A total of 170 patients with previous cerebrovascular events and suspected carotid artery stenoses underwent CDUS, blood-pool MRA, CTA and DSA. Accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for CDUS, FP MRA, SS MRA and CTA. The McNemar and Wilcoxon tests and receiver operating characteristic (ROC) curve analysis were used to determine significant differences (p<0.05) between the diagnostic performances of the four modalities, and the degree of stenosis was compared using linear regression. RESULTS: A total of 336 carotid bifurcations were studied. The area under the curve (AUC) for degree of stenosis was: CDUS 0.85±0.02, FP MRA 0.982±0.005, SS MRA 0.994±0.002 and CTA 0.997±0.001. AUC analysis showed no statistically significant difference between CTA and MRA (p=0.0174) and a statistically significant difference between CDUS and the other techniques (p<0.001). Plaque morphology analysis showed no significant difference between CTA and SS MRA; a significant difference was seen between CTA and SS MRA versus FP MRA (p=0.04) and CDUS (p=0.038). Plaque ulceration analysis showed a statistically significant difference between MRA and CTA (0.04< p<0.046) versus CDUS (p=0.019). CONCLUSIONS: CTA is the most accurate technique for evaluating carotid stenoses, with a slightly better performance than MRA (97% vs. 95% for SS MRA and 92% for FP MRA) and a greater accuracy than CDUS (97% vs. 76%). Blood-pool contrast-enhanced SS sequences offer improved evaluation of degree of stenosis and plaque morphology with accuracy substantially identical to CTA.

A comparison between SSMF and large-A(eff) Pure-Silica core fiber for ultra long-haul 100G transmission.

We compare the transmission performance of 112-Gb/s POLMUX-QPSK modulation over large-A(eff) Pure-Silica core fiber and SSMF using EDFA-only amplification. The higher nonlinear threshold of the large-A(eff) Pure-Silica core fiber allows for a 55% increase in transmission distance. By using back-propagation an additional 10% increase is observed. In case spans with equal length for both fiber types and two splices per span only would have been used, resulting in a lower span loss for the large-A(eff) Pure-Silica core fiber, the total increase grows to 85%.

Prospective comparative analysis of colour-Doppler ultrasound, contrast-enhanced ultrasound, computed tomography and magnetic resonance in detecting endoleak after endovascular abdominal aortic aneurysm repair.

OBJECTIVES: To assess the accuracy of colour-Doppler ultrasound (CDUS), contrast-enhanced ultrasonography (CEUS), computed tomography angiography (CTA) and magnetic resonance angiography (MRA) in detecting endoleaks after endovascular abdominal aortic aneurysm repair (EVAR). DESIGN: Prospective, observational study. MATERIALS AND METHODS: From December 2007 to April 2009, 108 consecutive patients who underwent EVAR were evaluated with CDUS, CEUS, CTA and MRA as well as angiography, if further treatment was necessary. Sensitivity, specificity, accuracy and negative predictive value of ultrasound examinations were compared with CTA and MRA as the reference standards, or with angiography when available. RESULTS: Twenty-four endoleaks (22%, type II: 22 cases, type III: two cases) were documented. Sensitivity and specificity of CDUS, CEUS, CTA, and MRA were 58% and 93%, 96% and 100%, 83% and 100% and 96% and 100% respectively. CEUS allowed better classification of endoleaks in 10, two and one patients compared with CDUS, CTA and MRA, respectively. CONCLUSIONS: The accuracy of CEUS in detecting endoleaks after EVAR is markedly better than CDUS and is similar to CTA and MRA. CEUS seems to be a feasible tool in the long-term surveillance after EVAR, and it may better classify endoleaks missed by other imaging techniques.

Low-dose contrast-enhanced time-resolved MR angiography at 3T: diagnostic accuracy for treatment planning and follow-up of vascular malformations.

AIM: To assess the accuracy of low-dose contrast-enhanced time-resolved 3T magnetic resonance angiography (MRA) for the morphological and functional assessment of vascular malformations (VM), and to evaluate its diagnostic potential for the depiction of treatment-induced changes. MATERIALS AND METHODS: Twenty-five patients with known VM underwent MRA to evaluate the location and extent of lesions and their haemodynamic characteristics. Three-dimensional (3D) T1-weighted time-resolved sequences were acquired following the administration of 0.05mmol/kg of gadobenate dimeglumine. VM were classified according to their morphology and haemodynamic characteristics. All patients thereafter underwent conventional angiography to confirm the diagnosis and to treat the lesions (embolization or sclerotherapy). Follow-up MRA was performed 30 days after treatment to assess morphological and functional changes. A visual analogue scale (VAS) was used to clinically assess the severity of symptoms before and after therapy. RESULTS: Based on haemodynamic characteristics, VM were classified as predominantly arterial [4 (16%)], artero-venous [19 (76%)] or venous [2 (8%)]. Twenty-three (92%) lesions were classified as high-flow VM and two (8%) as low-flow VM. Intralesional thrombosis was present in 17 (68%) lesions before therapy and in 10 lesions (40%) after therapy. The median VAS scores were 5±1 before treatment and 4±2 after treatment. Very good correlation (Spearman's correlation coefficient: rho=0.87; p=0.000) was noted between the reduction of lesion size on follow-up MRA and pain relief as assessed by VAS. CONCLUSION: Low-dose contrast-enhanced time-resolved 3T MRA can be used to define morphological and functional aspects of VM accurately during treatment planning and follow-up, and can identify post-therapy changes that positively correlate with treatment outcome.

Eating disorders and diabetic ketoacidosis in a pregnant woman with type 1 diabetes: a case report.

OBJECTIVE: To describe a case of diabetic ketoacidosis (DKA) in a pregnant woman with type 1 diabetes (T1DM) and disordered eating behaviour treated with a continuous subcutaneous insulin infusion, and to discuss some aspects of the monitoring and management of DKA in pregnancy and whether a pump is the safest therapeutic choice in the presence of some eating disorders. CASE REPORT: This 26-year-old Caucasian woman affected by T1DM was hospitalised during the last weeks of her fourth pregnancy because of DKA due to disordered eating. She was treated with a fluid infusion, intravenous insulin, and her electrolyte imbalance was carefully corrected. An elective cesarean section was performed after the correction of DKA in the 34th week (+6 days) of gestation. CONCLUSIONS: We suggest that pregnancy in T1DM women with eating disorders may not be rare. The prevention, early recognition and aggressive management of DKA can minimise the possible complications, and is mandatory for the safety of the fetus and mother.

[Epidemiology of work-related accidents in the Lazio Region of Italy]. / Epidemiologia degli infortuni sul lavoro nella Regione Lazio.

BACKGROUND: Prevention of work-related accidents requires an in-depth epidemiological assessment of the issue. In Italy the most used databases are from the national insurance (INAIL) and research (ISPESL) institutes. However, these data are only available several years after the time of accident. OBJECTIVES: To describe the characteristics of accidents and evaluate factors potentially associated with hospitalization using the Information System of Hospital Emergency Departments (SIES). METHODS: We analyzed 51.705 Emergency Department (ED) work-related accident admissions in the Lazio Region of Italy in 2008 among workers aged 16-65 years. Information on socio-demographics, diagnosis, triage codes, and outcome of ED admissions were gathered. We performed a logistic regression model to estimate association between these factors and risk of hospitalization after ED admission. RESULTS: The subjects' mean age was 39.1 (SD 11.0); 71.5% woere men, 12.7% were foreigners, 5.9% arrived by ambulance, 4.5% with triage red/yellow tags, 2.7% were hospitalized. Diagnosis was trauma in 85.1%, orthopaedic lesions in 8.3%. We found a higher risk of hospitalization in subjects with: one year of age increase (OR=1.02; 95% CIs: 1.01-1.03), males (OR=1.68; 95% CIs: 1.44-1.97), foreigners coming from countries with high emigration rates (OR=1.55; 95% CIs: 1.31-1.82), ED triage red/yellow tags (OR=84.47; 95% CIs: 47.06-151.60). CONCLUSIONS: It was confirmed that data fr-om an emergency health care information system can be a useful complement to information gathered by national insurance and research institutes, thus resolving the limit posed by the delay in availability for analysis of these data after the occurrence of accidents. We also identified some factors potentially associated with more serious accidents, which constitute a basis for planning and implementing specific public health preventive interventions.

Preliminary experience with MRA in evaluating the degree of carotid stenosis and plaque morphology using high-resolution sequences after gadofosveset trisodium (Vasovist) administration: comparison with CTA and DSA.

PURPOSE: The authors performed a preliminary study with blood-pool contrast-enhanced magnetic resonance angiography (MRA) in evaluating the degree of carotid artery stenosis and plaque morphology, comparing the diagnostic performance of first-pass (FP) and steady-state (SS) acquisitions with 64-slice computed tomography angiography (CTA) and using digital subtraction angiography (DSA) as the reference standard. MATERIALS AND METHODS: Twenty patients with >or=50% carotid artery stenosis at Doppler sonography underwent blood-pool contrast-enhanced MRA, CTA and DSA. Two independent radiologists evaluated MRA and CTA examinations to assess the degree of stenosis and characterise plaque morphology. Accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for FP, SS and CTA. The McNemar and Wilcoxon tests were used to determine significant differences (p<0.05) between the diagnostic performance of the three modalities. RESULTS: Forty carotid bifurcations were studied. For stenosis grading, accuracy, sensitivity, specificity, PPV and NPV were 90%, 89%, 90%, 89% and 90%, respectively, at FP; 95%, 95%, 95%, 95% and 95%, respectively, at SS; and 97.5%, 95%, 100%, 100% and 95%, respectively, at CTA. SS and CTA were superior to FP for evaluating the degree of stenosis (p<0.05). For evaluating plaque morphology, accuracy, sensitivity, specificity, PPV and NPV were 87.5%, 89%, 86%, 85% and 90%, respectively, at FP; 97.5%, 100%, 95%, 95% and 100%, respectively, at SS; and 100%, 100%, 100%, 100% and 100%, respectively, at CTA. There were no significant differences between FP, SS and CTA for plaque assessment (p>0.05). CONCLUSIONS: Blood-pool contrast-enhanced MRA with SS sequences allow improved diagnostic evaluation of the degree of carotid stenosis and plaque morphology compared with FP and is substantially equal to CTA and DSA.

Dysfunctional DC subsets in RCC patients: ex vivo correction to yield an effective anti-cancer vaccine.

Dendritic cells (DCs) are potent antigen-presenting cells responsible for the activation and functional polarization of specific T cells. In patients with renal cell carcinoma (RCC) and other cancers, coordinate DC and T cell defects have been reported. In particular, DC and T cell functional subsets that are not conducive to tumor clearance are hypothesized to predominate in patients with advanced-stage disease. Two major peripheral blood DC subsets have been identified in humans: myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) that are believed to mediate contrasting effects on cancer immunity. Given the lack of information regarding DC subsets in patients with RCC, in the present study we have investigated the comparative frequencies and activation states of mDC and pDC in peripheral blood, cancer tissues and lymph nodes of patients with RCC using flow cytometry and immunohistochemistry. Three monoclonal antibodies (mAbs) reactive against specific DC subsets (BDCA-2 or BDCA-4 for pDC and BDCA-1 and BDCA-3 which represent two distinct subsets of mDC, mDC1 and mDC2, respectively) were employed. We observed a significant reduction of both DC subsets in the peripheral blood of patients as compared to normal donors. Similarly, both mDC and pDC were recruited in large numbers into RCC tumor tissues, where they displayed an immature phenotype (DC-LAMP(-)) and appeared unable to differentiate into mature DC (CD83(+)) that were competent to migrate to draining lymph nodes. However, we were readily able to generate ex vivo mDC from RCC patients. These DC stimulated robust anti-tumor CTL in vitro and would be envisioned for use in DC-based vaccines applied in patients with RCC whose existing immune system is judged dysfunctional, anergic or prone to undergo apoptosis.