Electrophysiological Correlates of Reward Anticipation in Subjects with Schizophrenia: An ERP Microstate Study.

The current study aimed to investigate alterations of event-related potentials (ERPs) microstate during reward anticipation in subjects with schizophrenia (SCZ), and their association with hedonic experience and negative symptoms. EEG data were recorded in thirty SCZ and twenty-three healthy controls (HC) during the monetary incentive delay task in which reward, loss and neutral cues were presented. Microstate analysis and standardized low-resolution electromagnetic tomography (sLORETA) were applied to EEG data. Furthermore, analyses correlating a topographic index (the ERPs score), calculated to quantify brain activation in relationship to the microstate maps, and scales assessing hedonic experience and negative symptoms were performed. Alterations in the first (125.0-187.5 ms) and second (261.7-414.1 ms) anticipatory cue-related microstate classes were observed. In SCZ, reward cues were associated to shorter duration and earlier offset of the first microstate class as compared to the neutral condition. In the second microstate class, the area under the curve was smaller for both reward and loss anticipation cues in SCZ as compared to HC. Furthermore, significant correlations between ERPs scores and the anticipation of pleasure scores were detected, while no significant association was found with negative symptoms. sLORETA analysis showed that hypo-activation of the cingulate cortex, insula, orbitofrontal and parietal cortex was detected in SCZ as compared to HC. Abnormalities in ERPs could be traced already during the early stages of reward processing and were associated with the anticipation of pleasure, suggesting that these dysfunctions might impair effective evaluation of incoming pleasant experiences. Negative symptoms and anhedonia are partially independent results.

Premorbid academic and social functioning in patients with schizophrenia and its associations with negative symptoms and cognition.

OBJECTIVE: The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. METHOD: Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. RESULTS: We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). CONCLUSION: Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Species and antimicrobial susceptibility testing of coagulase-negative staphylococci in periprosthetic joint infections.

The objective was to evaluate the distribution of coagulase-negative staphylococci (CNS) involved in periprosthetic-joint infections (PJIs) and to describe their susceptibility profile to antibiotics. We conducted a multicentre retrospective study in France, including 215 CNS PJIs between 2011 and 2015. CNS PJIs involved knees in 54% of the cases, hips in 39%, other sites in 7%. The distribution of the 215 strains was: Staphylococcus epidermidis 129 (60%), Staphylococcus capitis 24 (11%), Staphylococcus lugdunensis 21 (10%), Staphylococcus warneri 8 (4%), Staphylococcus hominis 7 (3%), Staphylococcus haemolyticus 7 (3%). More than half of the strains (52.1%) were resistant to methicillin, 40.9% to ofloxacin, 20% to rifampicin. The species most resistant to antibiotics were S. hominis, S. haemolyticus, S. epidermidis, with 69.7% of the strains resistant to methicillin and 30% simultaneously resistant to clindamycin, cotrimoxazole, ofloxacin and rifampicin. No strain was resistant to linezolid or daptomycin. In this study on CNS involved in PJIs, resistance to methicillin is greater than 50%. S. epidermidis is the most frequent and resistant species to antibiotics. Emerging species such S. lugdunensis, S. capitis and Staphylococcus caprae exhibit profiles more sensitive to antibiotics. The antibiotics most often active in vitro are linezolid and daptomycin.

Joint infection due to Raoultella planticola: first report.

The genus Raoultella has been separated from the genus Klebsiella in 2001. Two main species are responsible for human infections: R. ornithinolytica and R. planticola. The most frequent infections due to R. planticola include cystitis, pneumonia and bacteremia (mostly in immunocompromised hosts). To date, no joint or bone infection has been reported. We describe the first case of septic arthritis due to R. planticola following an arthroscopy with intra-articular injection of corticosteroids. Evolution was favorable after arthroscopic lavage and antibiotic therapy with quinolones. Raoultella planticola has been described rarely in human infection. It is mainly deemed responsible for cystitis, pneumonia and bacteremia (mostly in immunocompromised hosts) [1-3]. To our knowledge no case of bone or joint infection has been reported. We described here the first case of infective arthritis due to R. planticola involving a native knee joint following synovectomy and intra-articular injection of corticosteroids during arthroscopy.

Pathogenesis of chronic cluster headache and bouts: role of tryptamine, arginine metabolism and α1-agonists.

The aim of this study was to explore the possible role of tryptamine in the pathogenesis of chronic cluster headache along with that of adrenaline and noradrenaline (α-agonists) together with arginine metabolism in the origin of cluster bouts. Plasma levels of tyramine, tryptamine, serotonin, 5-hydroxyindolacetic acid, noradrenalin, adrenalin and the markers of arginine metabolism such as arginine, homoarginine, citrulline, ADMA and NMMA, were measured in 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster) and 28 control subjects. The plasma levels of tyramine, tryptamine, noradrenalin and adrenalin were found several times higher in chronic cluster headache patients compared to controls, whereas the plasma levels of arginine, homoarginine and citrulline were significantly lower. No differences were found in the plasma levels of serotonin, 5-hydroxyindolacetic, ADMA and NMMA between chronic cluster headache patients and control subjects. These results provide support for a role of tryptamine in the pathogenesis of chronic cluster headache and, in particular, in the duration of the cluster bouts. In addition, the low levels of the nitric oxide substrates together with the high levels of noradrenalin and adrenalin suggest an activation of endothelial TAAR1 receptors followed by the release of nitric oxide in the circulation that may constitute the final step of the physiopathology of cluster crisis.

Exhaled nitric oxide dynamics in asthmatic reactions induced by diisocyanates.

BACKGROUND: Isocyanate-induced asthmatic reactions are associated with delayed increase in fractional exhaled nitric oxide measured at expiratory flow of 50 mL/s (FeNO50), a biomarker of airway inflammation. The time course of FeNO increase is compatible with the activation of NO synthase, but the origin of NO production in the lung is undetermined. OBJECTIVE: The aim of this study was to define the dynamics of airway and alveolar NO during specific inhalation challenge (SIC) with isocyanates and the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. METHODS: Spirometry, exhaled NO parameters (FeNO50, bronchial wall NO concentration, NO airway diffusing capacity, NO flux to luminal space, alveolar NO) and ADMA levels in exhaled breath condensate were measured before and at intervals up to 24 h after exposure to isocyanates. The results were compared between 17 SIC-positive and eight SIC-negative subjects. RESULTS: A significant FeNO50 increase in SIC-positive subjects was detected 24 h after exposure and was associated with the augmented NO flux from airway wall to the lumen, whereas airway NO diffusion and alveolar NO were not affected. The changes in NO dynamics were specific for the subjects who developed an asthmatic reaction, but were independent from the pattern and magnitude of bronchoconstriction. There was no evidence that exhaled NO is modulated by the changes in ADMA concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Because isocyanate-induced increase in FeNO50 was almost exclusively determined by the increase in NO flux, the use of FeNO50 appears adequate to monitor the exhaled NO dynamics during SIC. FeNO50 measurement may provide additional information to spirometry, because bronchoconstriction and airway inflammatory responses are dissociated.

A case of placental site nodule associated with cervical high-grade squamous intraepithelial lesion.

INTRODUCTION: A placental site nodule (PSN) is a remnant of intermediate trophoblast (extravillous trophoblast, EVT) from a previous pregnancy. Usually, this a benign lesion, which once removed, does not require any treatment and does not recur. Although this lesion is related to pregnancy, it may be detected many months or several years after the pregnancy from which it resulted. The lesion represents a degenerative process of EVT. Especially in tissue obtained from curettage, can microscopically mimic aggressive lesions of intermediate trophoblast, such as placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT), and in an unusual location can pose problems in differential diagnosis with other malignancies, as in the present cervical example. CASE REPORT: A 36-year-old female, gravida 2, para 1, with a history of early spontaneous abortion two years prior, was submitted to a cervical smear for abnormal uterine bleeding, which showed a cervical high squamous intraepithelial lesion (HSIL) with extension to the endocervical cells. Histologic examination of the endocervical curettage revealed haphazardly distributed fragments of tissue, showing extensive hyalinization and cells of different size with indistinct outlines, organized in small groups, singly, or in cords. Mitotic figures were absent. Immunohistochemical analysis revealed focal positivity to cytokeratin 8 (CK8) and placental alkaline phosphatase and negativity to high molecular weight cytokeratin. The Ki-67 index was low. As a result, the morphological and immunohistochemical findings led to the diagnosis of a PSN. CONCLUSION: Diagnosis of a PSN in an unusual location also can pose problems in differential diagnosis with other malignancies, as in the present cervical example. In the present case, the cervical location and the association with HSIL might suggest an erroneous diagnosis of cervical invasive squamous carcinoma. Clinical and pathological data, with immunohistochemical study, are mandatory for a correct diagnosis of this lesion.

The association between cannabis abuse and subsequent schizophrenia: a Swedish national co-relative control study.

BACKGROUND: Although cannabis abuse (CA) is known to be associated with schizophrenia, the causal nature of this association is unclear, with prodromal effects complicating its interpretation. METHOD: From Swedish national registry databases, we used a co-relative case-control design with full-sibling, half-sibling and first-cousin comparisons, alongside a general Swedish population sample. Using ICD codes, 5456 individuals with an initial diagnosis of schizophrenia (2000-2010) were matched with five schizophrenia-free controls. We further identified first-cousin, half-sibling and full-sibling pairs discordant for CA and statistically extrapolated results for discordant monozygotic (MZ) twins. RESULTS: Within the general Swedish population, CA was strongly associated with later schizophrenia [odds ratio (OR) 10.44, 95% confidence interval (CI) 8.99-12.11]. This association was substantially attenuated both by increasing temporal delays between CA exposure and schizophrenia diagnosis and by controlling for increasing degrees of familial confounding. Extrapolated discordant MZ pairs suggested that fully controlling for confounding familial factors reduced the association between CA and later schizophrenia to more modest levels (ORs of approximately 3.3 and 1.6 with 3- and 7-year temporal delays respectively). Opiate, sedative, cocaine/stimulant and hallucinogen abuse were also strongly associated with subsequent schizophrenia in the general population. After controlling for familial confounding, only cocaine/stimulant exposure remained associated. CONCLUSIONS: CA has an appreciable causal impact on future risk for schizophrenia. However, population-based estimates of cannabis-schizophrenia co-morbidity substantially overestimate their causal association. Predictions of the cases of schizophrenia that might be prevented by reduced cannabis consumption based on population associations are therefore likely to be considerably overestimated.

Synergistic interactions between PBDEs and PCBs in human neuroblastoma cells.

Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants. Exposure to these chemicals has been associated with developmental neurotoxicity, endocrine dysfunction, and reproductive disorders. Humans and wildlife are generally exposed to a mixture of these environmental pollutants, highlighting the need to evaluate the potential effects of combined exposures. In this study, we investigated the cytotoxic effects of the combined exposure to two PBDEs and two PCBs in a human neuronal cell line. 2,2',4,4'-Tetrabromodiphenyl ether, 2,2',4,4',5-pentabromodiphenyl ether, PCB-126 (3,3',4,4',5-pentachlorobiphenyl; a dioxin-like PCB), and PCB-153 (2,2',4,4',5,5'-hexachlorobiphenyl; a non-dioxin-like PCB) were chosen, because their concentrations are among the highest in human tissues and the environment. The results suggest that the nature of interactions is related to the PCB structure. Mixtures of PCB-153 and both PBDEs had a prevalently synergistic effect. In contrast, mixtures of each PBDE congener with PCB-126 showed additive effects at threshold concentrations, and synergistic effects at higher concentrations. These results emphasize the concept that the toxicity of xenobiotics may be affected by possible interactions, which may be of significance given the common coexposures to multiple contaminants.

Asthma severity in childhood and metabolomic profiling of breath condensate.

BACKGROUND: Asthma is a heterogeneous disease and its different phenotypes need to be better characterized from a biochemical-inflammatory standpoint. This study aimed to apply the metabolomic approach to exhaled breath condensate (breathomics) to discriminate different asthma phenotypes, with a particular focus on severe asthma in children. METHODS: In this cross-sectional study, we recruited 42 asthmatic children (age, 8-17 years): 31 with nonsevere asthma (treated with inhaled steroids or not) and 11 with severe asthma. Fifteen healthy children were enrolled as controls. Children performed exhaled nitric oxide measurement, spirometry, exhaled breath condensate (EBC) collection. Condensate samples were analyzed using a metabolomic approach based on mass spectrometry. RESULTS: A robust Bidirectional-Orthogonal Projections to Latent Structures-Discriminant Analysis (O2PLS-DA) model was found for discriminating both between severe asthma cases and healthy controls (R(2)  = 0.93; Q(2)  = 0.75) and between severe asthma and nonsevere asthma (R(2)  = 0.84; Q(2)  = 0.47). The metabolomic data analysis leads to a robust model also when the 3 groups of children were considered altogether (K = 0.80), indicating that each group is characterized by a specific metabolomic profile. Compounds related to retinoic acid, adenosine and vitamin D (Human Metabolome Database) were relevant for the discrimination between groups. CONCLUSION: The metabolomic profiling of EBC could clearly distinguish different biochemical-metabolic profiles in asthmatic children and enabled the severe asthma phenotype to be fully discriminated. The breathomics approach may therefore be suitable for discriminating between different asthma metabolic phenotypes.

A case of ovarian psammocarcinoma with homolateral serous cystoadenofibroma and thecoma associated with Brenner tumour and cystoadenofibroma of the contralateral ovary.

Psammocarcinoma of the ovary is a rare serous neoplasm, with only 32 cases reported in the international literature. Characteristically, this tumour shows extensive formation ofpsammoma bodies, low-grade cytological features, and invasion of the ovarian stroma, peritoneum or intraperitoneal viscera. The behaviour of this entity is unpredictable, with benign, low malignant and metastatic potential. Herein the authors report a case ofpsammocarcinoma of the ovary with homolateral serous cystoadenofibroma and thecoma, which were associated with Brenner tumour and adenofibroma of the contralateral ovary, in a 78-year-old woman. Thus, this example shows an unpredictable tumour associated with multiple benign epithelial neoplasms and a benign stromal tumour. Moreover, this example of psammocarcinoma is very interesting because it measures only 1.5 x 0.5 x 1.5 cm and, to the best of the author's knowledge, represents the smallest case ofpsammocarcinoma described so far in the literature.

Can we rely on histopathological results for the diagnosis of prosthetic joint infection?

BACKGROUND: Histopathology is one of the diagnostic criteria for prosthetic joint infection (PJI) proposed by all academic societies. The aim of this study was to compare histopathological and microbiological results from samples taken intraoperatively at the same site in patients with suspected or proven PJI. PATIENTS AND METHODS: We conducted a monocenter retrospective study including all patients having undergone surgery from 2007 to 2015 with suspected or proven PJI. During surgery, both histopathological and microbiological samples were taken. Patients with a history of antimicrobial treatment 2 weeks prior to surgery were excluded. We considered as major criteria and gold standard for PJI diagnosis the presence of a sinus tract communication and/or the same microorganism in at least two cultures. RESULTS: Finally, 181 patients who underwent 309 surgeries were included. The median number of samples per surgery was 4 (interquartile range (IQR) = 3-5) for histopathology and 5 (IQR = 4-6) for microbiology. Major criteria were observed in 177 patients (57.3%), while positive histology in at least one intraoperative sample was present in 119 (38.5%). The concordance was 74%. The sensitivity and specificity of histopathology were 61% and 92% respectively. Available "histopathology-culture" sample pairs numbered 1247. Among them, positive histopathology was found in 292 samples (23%) and culture in 563 (45%). Concordance was 64%. The highest correlation was observed for very early infection (<1 month) (OR: 9.1, 95% CI: 3.6-23) and for virulent microorganisms, such as Staphylococcus aureus (OR: 7.8, 95% CI: 5.2-11.8), Streptococci (OR:7.8; 95% CI: 4-15.2) or Enterobacterales (OR: 7.4; 95% CI: 4.2-13.1). CONCLUSION: Histopathologic examination is a valuable criterion for PJI diagnosis, but it may lack sensitivity for chronic infections or due to low-virulence pathogens.

Third whole-brain radiation therapy for multiple brain metastases. Should it be considered in selected patients?

Whole brain reirradiation for the treatment of multiple brain metastases has shown promising results. However, concerns remain over the possible neurotoxic effects of the cumulative dose as well as the questionable radiosensitivity of recurrent metastases. A second reirradiation of the whole brain is ordinarily performed in our department for palliative purposes in patients presenting with multiple metastatic brain progression. For this study, an investigational third whole brain reirradiation has been administered to highly selected patients to obtain disease control and delay progression. Clinical outcomes and neurological toxicity were also evaluated.

Asthma, allergy and respiratory infections: the vitamin D hypothesis.

The recent discovery that every tissue in the human body has vitamin D receptors and that vitamin D has pleiotropic effects has prompted an increased interest in this hormone. Vitamin D deficiency is widespread and on the increase. There is no consensus on the serum vitamin D levels to consider appropriate for global health, the cutoffs for its deficiency, or the doses to use for its supplementation. Vitamin D seems to correlate closely with host reactions against various respiratory infections. Epidemiological studies have shown that low serum 25-hydroxyvitamin D levels are associated with a higher risk of upper and lower respiratory infections in children and a shortage of vitamin D may contribute to asthmatic patients' symptoms and morbidity rates. There are studies highlighting associations between childhood asthma, fetal lung and/or immune development, and maternal vitamin D intake. An insufficiency of this vitamin also seems to be implicated in the onset of childhood atopy and food allergies. The hypothesis is that vitamin D could have a central role in these pathological situations and that it may represent a novel preventive and/or therapeutic strategy. This article reviews and discusses published data on the relationship between vitamin D and asthma and allergy, emphasizing the need for controlled, prospective studies on vitamin D supplementation to clarify whether it has a role in the prevention of and treatment for asthma and allergic conditions.

No benefit from carotid intervention in fatal stroke prevention for >80-year-old patients.

BACKGROUND: Invasive management of patients ≥80 years of age with carotid stenosis may be questionable. The higher likelihood of stroke needs to be balanced with the increased perioperative risk and the reduced life expectancy of this ageing population. The purpose of this study was to evaluate the clinical relevance of carotid stenosis revascularisation in octogenarians. METHODS: All patients ≥80 years of age who received carotid revascularisation in 2001-2010 were reviewed for perioperative and 5-year outcomes. The experience was comprehensive of carotid endarterectomy (CEA) and carotid stenting (CAS) performed during the training frame when age was not a contraindication for this procedure. Mortality rates were compared to those of octogenarians of the same geographical territory according to all-cause and stroke-related mortality national statistics datasets. RESULTS: A total of 348 procedures performed in ≥80-year-old patients (272 males) were reviewed: 162 (46.6%) were by CAS and 169 (48.6%) were for symptomatic disease. Perioperative stroke/death rate was 5.5% and was non-significantly higher for symptomatic disease (7.1% vs. 3.9% asymptomatic; p = 0.24), after CAS (6.2% vs. 4.8% CEA; p = 0.64) and in females (6.6% vs. 5.1% males; p = 0.57). At median follow-up of 36.18 months, 95 deaths and 21 new ischaemic strokes (12 fatal) occurred with 5-year Kaplan-Meier freedom from stroke of 84.8% (78.7%, symptomatic vs. 90.3% asymptomatic; p = 0.003). According to national datasets, in 80-85-year-old resident population 5-year mortality was 29.9% (23.4% females, 40.6% males) and ischaemic stroke-related mortality was 14.9% (16.8% females, 13.0% males). Corresponding figures from treated population showed a 5-year mortality of 49.4%, higher in males (39.5% females, 52.5% males) and ischaemic stroke-related mortality of 20.2%, higher in females (40.0% females, 15.6% males). Comparing data from the study population with residents' figures, ischaemic stroke-related mortality hazard was significantly higher in the study females: odds ratio (OR) 3.2, 95% confidence interval (CI) 1.16-9.17; p = 0.029 (for males: OR 0.97, 95%CI 0.89-1.10; p = 0.99). CONCLUSIONS: Despite perioperative stroke/death risks being lower compared with CAS, the benefit of surgical carotid revascularisation in old patients remains controversial due to limited life expectancy and high fatality of stroke in this ageing population. Invasive treatment of carotid stenosis may not be warranted in most patients ≥80 years of age with carotid stenosis, especially when female and asymptomatic.

Prosthetic carotid bypass graft for in-stent restenosis performed for post-endarterectomy recurrent stenosis: technical details.

AIM: Carotid artery stenting (CAS) is the treatment of choice for recurrent stenosis after carotid endarterectomy (CEA). However a significative incidence of in-stent restenosis could be occurred. Despite classical CEA leads to good results, in selective cases bypass graft may be the best treatment of in-stent restenosis. CASE REPORTS: We describe two cases of carotid bypass graft performed to treat a recurrent in-stent stenosis after CAS for post-CEA restenosis. No death and cardiac complication occurred and no cranial nerves impairment was detected. CONCLUSION: Prosthetic bypass graft is safe and effective in treatment of in-stent recurrent restenosis after CEA restenosis.

Second-generation thienopyridine use is not associated with better early perioperative outcome during carotid stenting.

OBJECTIVE: Management of anti-platelet therapy during carotid artery stenting (CAS) is mainly based on indirect evidence from coronary stenting experience. There is common agreement on the use of thienopyridine (mainly second-generation) during CAS, but some patients are unsuitable for clopidogrel treatment and data on the benefit of its use in large CAS populations are lacking. The aim of this study was to investigate whether clopidogrel was associated with reduced perioperative morbidity in patients undergoing CAS. METHODS: Consecutive patients undergoing CAS for primary carotid stenosis from 2004 to 2009 were reviewed. The independent association of clopidogrel and perioperative morbidity was assessed using multivariable analysis. RESULTS: A total of 1083 patients were treated (29% females, mean age 71.6 years); 825 (76%) patients were given clopidogrel starting before treatment. Clopidogrel use was associated with a non-significant reduction of perioperative stroke/death (4.3% vs. 2.4%; p = 0.13) and disabling stroke (1.2% vs. 1.0%; p = 1) rates. The non-significant stroke/death difference was similar in symptomatic (5.8% vs. 4.0%, p = 0.37) and asymptomatic (3.7% vs. 1.9%; p = 0.17) patients. After adjusting for demographics, co-morbidities and other therapies with multivariable analysis, clopidogrel use failed to show any significant independent association in decreasing operative risks. The only independent protective factor was use of statins (p = 0.010). The additional use of dual anti-platelet therapy did not add any advantage to the use of clopidogrel alone. CONCLUSIONS: The suggested benefit of clopidogrel in decreasing the incidence of complications in patients undergoing CAS may be overestimated due to the overlapping effect of other more relevant factors (e.g., pleiotropy and plaque stabilisation from statins). More data and level I evidence are needed to understand which is the best medical management of CAS that will help improve outcomes of the procedure.

The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas.

The oncoprotein of simian virus-40, SV40 large T-antigen (Tag), is reported to target and to inactivate growth suppressive proteins such as the retinoblastoma family and p53 (ref. 4, 5), leading to transformation of human cell lines in vitro, tumor production in rodents, and detection of Tag in several human cancers including mesotheliomas. The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner, have cell growth suppressive properties and bind to specific members of the E2F family and various cyclins. Even though mesotheliomas are among the most aggressive human cancers, alterations of important cell-cycle "controllers," such as the Rb family genes, have never been reported in these tumors. We found the presence of SV40-like sequences in 86% of 35 archival specimens of mesothelioma. We also demonstrated that SV40 Tag, isolated from frozen biopsies of human mesothelioma, binds each of the retinoblastoma family proteins, pRb, p107 and pRb2/p130, in four of four specimens. We propose that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumor and/or growth suppressive proteins.

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference.

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet-based process with a final meeting on 28 June 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, the use of pre-operative intra-aortic balloon counterpulsation, and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.