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Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/bIuRhGQsUjs

The association between elevated liver enzymes or FIB-4 (fibrosis index 4) and outcome in patients with venous thromboembolism (VTE) has not been evaluated. Data from patients in RIETE (Registro Informatizado Enfermedad TromboEmbólica) were used to assess the association between elevated liver enzymes or FIB-4 levels and the rates of major bleeding or death in apparent liver disease-free patients with acute VTE under anticoagulation therapy. A total of 6206 patients with acute VTE and without liver disease were included. Of them, 92 patients had major bleeding and 168 died under anticoagulation therapy. On multivariable analysis, patients with elevated liver enzymes were at increased mortality risk (HR: 1.58; 95% CI: 1.10–2.28), while those with FIB-4 levels > 2.67 points were at increased risk for major bleeding (HR: 1.69; 95% CI: 1.04–2.74). Evaluation of liver enzymes and FIB-4 index at baseline in liver disease-free patients with VTE may provide additional information on the risk for major bleeding or death during anticoagulation. Supplementary Information The online version contains supplementary material available at 10.1007/s11739-021-02858-x.

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90‐day and 1‐year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90‐day all‐cause (odds ratio [OR], 2.81; 95% CI, 2.33–3.38) and PE‐related mortality (OR, 2.38; 95% CI, 1.37–4.14) and increased 1‐year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10–9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all‐cause mortality (OR, 1.91; 95% CI, 1.57–2.32) but not PE‐related mortality (OR, 1.50; 95% CI, 0.85–2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90‐day all‐cause (OR, 2.28; 95% CI, 1.75–2.97) and PE‐related (OR, 3.64; 95% CI, 2.01–6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.

The coronavirus disease (COVID‐19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella‐like eruption, representing an additional effect of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, as commonly observed in other viral diseases. Considering that symptomatic patients with COVID‐19 generally undergo multidrug treatments, the occurrence of a possible adverse drug reaction presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59‐year‐old Caucasian woman, affected by a stable form of chronic lymphocytic leukemia, and symptomatic SARS‐CoV‐2 infection, treated with a combination of hydroxychloroquine sulfate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high‐flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin were continued and the patient received a high‐dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID‐19 disease‐related cutaneous manifestations, where is justified to continue the multidrug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start appropriate antiallergic treatment., The coronavirus disease (COVID‐19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella‐like eruption, representing an additional effect of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, as commonly observed in other viral diseases. Considering that symptomatic patients with COVID‐19 generally undergo multidrug treatments, the occurrence of a possible adverse drug reaction presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59‐year‐old Caucasian woman, affected by a stable form of chronic lymphocytic leukemia, and symptomatic SARS‐CoV‐2 infection, treated with a combination of hydroxychloroquine sulfate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high‐flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin and received a high‐dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID‐19 disease‐related cutaneous manifestations, where is justified to continue the multi‐drug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start appropriate antiallergic treatment.

To evaluate the efficacy, safety, and tolerability of switching to a dolutegravir (DTG)-based regimen in a cohort of virological suppressed HIV-infected patients who have previously been treated with different antiretroviral combination. The dynamics of total HIV-DNA and levels of high-sensitivity c-reactive protein, interleukin-6, soluble-CD14, and D-Dimer were also analyzed. Ninety-six individuals who switched to a DTG-containing regimen were followed up for 48 weeks. HIV RNA, CD4+ T cell count, weight, and levels of laboratory parameters were recorded at baseline, after 24 and 48 weeks of treatment for all study participants. In a subgroup of patients, HIV DNA and inflammation/coagulation marker levels were also analyzed until week 24. Ninety-three out of 96 patients maintained virological suppression, including patients who switched to dual-therapy from triple-drug combination. Eighteen out of 96 patients had residual viremia at baseline, of which 13 reached the maximal viral suppression at W48. Serum creatinine levels showed a significant increase at weeks 24 and 48. A progressive reduction of total cholesterol was observed from week 24 and up to week 48. No variation in body mass index was detected. HIV DNA, inflammation, and coagulation marker levels did not significantly change during follow-up. Switching to a DTG-based regimen may be a key option for achieving and maintaining maximal virological suppression, even in patients showing residual viremia at baseline. Furthermore, the improvement in blood lipid profile and the overall tolerability observed in this study strongly support the use of these regimens in the aging HIV population.

The coronavirus disease (COVID-19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella-like eruption, representing an additional effect of the SARS-CoV-2 infection, as commonly observed in other viral diseases. Considering that symptomatic COVID-19 patients generally undergo multi-drug treatments, the occurrence of a possible adverse drug reaction (ADR) presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59-year-old Caucasian woman, affected by a stable form of Chronic lymphocytic leukaemia, and symptomatic SARS-CoV.2 infection, treated with a combination of hydroxychloroquine sulphate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high-flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin and received a high-dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID-19 disease-related cutaneous manifestations, where is justified to continue the multi-drug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start an appropriate treatment.

Background MRI plays a crucial role to identify men with a high likelihood of clinically significant prostate cancer who require immediate biopsy. The added value of DCE MRI in combination with T2-weighted imaging and DWI is controversial (risks related to gadolinium administration, duration of MR exam, financial burden, effects on diagnostic performance). A comparison of a biparametric and a standard multiparametric MR imaging protocol, taking into account the different experience of the readers, may help to choose the best MR approach regarding diagnostic performance. Purpose To determine the added value of dynamic contrasted-enhanced imaging (DCE) over T2-weighted imaging (T2-WI) and diffusion weighted imaging (DWI) for the detection of clinically significant prostate cancer, and to evaluate how it affects the diagnostic performance of three readers with different grade of experience in prostate imaging. Materials and methods Eighty-five patients underwent prostate MR examination at 1.5 T MR scanner performed because of elevated prostate-specific antigen level and/or suspicion of prostate cancer at digital rectal examination. Two MR images sets (Set 1 = biparametric, Set 2 = multiparametric) were retrospectively and independently scored by three radiologists with 7, 3 and 1 years of experience in prostate MR imaging respectively, according to PI-RADS v2. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated by dichotomizing reader scores. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUCs) were calculated for each reader and image set. A comparison of ROC curves was performed to test the difference between the areas under the ROC curves among the three readers. Results There was no significant difference regarding the detection of clinically significant tumor among the three readers between the two image sets. The AUC for the bi-parametric and multi-parametric MR imaging protocol was respectively 0.68–0.72 (Reader 1), 0.72–0.70 (Reader 2) and 0.60–0.54 (Reader 3). ROC curve comparison revealed no statistically significant differences for each protocol among the most experienced (Reader 1) and the other readers (Readers 2–3). Conclusion The diagnostic accuracy of a bi-parametric MR imaging protocol consisting of T2-weighted imaging and DWI is comparable with that of a standard multi-parametric imaging protocol for the detection of clinically significant prostate cancer. The experience of the reader does not significantly modify the diagnostic performance of both MR protocols.

Here we evaluated the hypothesis that resting state electroencephalographic (EEG) cortical sources correlated with cognitive functions and discriminated asymptomatic treatment-naïve HIV subjects (no AIDS).EEG, clinical, and neuropsychological data were collected in 103 treatment-naïve HIV subjects (88 males; mean age 39.8 years ± 1.1 standard error of the mean, SE). An age-matched group of 70 cognitively normal and HIV-negative (Healthy; 56 males; 39.0 years ± 2.0 SE) subjects, selected from a local university archive, was used for control purposes. LORETA freeware was used for EEG source estimation in fronto-central, temporal, and parieto-occipital regions of interest.Widespread sources of delta (4 Hz) and alpha (8-12 Hz) rhythms were abnormal in the treatment-naïve HIV group. Fronto-central delta source activity showed a slight but significant (p 0.05, corrected) negative correlation with verbal and semantic test scores. So did parieto-occipital delta/alpha source ratio with memory and composite cognitive scores. These sources allowed a moderate classification accuracy between HIV and control individuals (area under the ROC curves of 70-75%).Regional EEG abnormalities in quiet wakefulness characterized treatment-naïve HIV subjects at the individual level.This EEG approach may contribute to the management of treatment-naïve HIV subjects at risk of cognitive deficits.

This study tested a simple statistical procedure to recognize single treatment-naïve HIV individuals having abnormal cortical sources of resting state delta (4 Hz) and alpha (8-13 Hz) electroencephalographic (EEG) rhythms with reference to a control group of sex-, age-, and education-matched healthy individuals. Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values were expected to show worse cognitive status.Resting state eyes-closed EEG data were recorded in 82 treatment-naïve HIV (39.8 ys.±1.2 standard error mean, SE) and 59 age-matched cognitively healthy subjects (39 ys.±2.2 SE). Low-resolution brain electromagnetic tomography (LORETA) estimated delta and alpha sources in frontal, central, temporal, parietal, and occipital cortical regions.Ratio of the activity of parietal delta and high-frequency alpha sources (EEG marker) showed the maximum difference between the healthy and the treatment-naïve HIV group. Z-score of the EEG marker was statistically abnormal in 47.6% of treatment-naïve HIV individuals with reference to the healthy group (p0.05). Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values exhibited lower mini mental state evaluation (MMSE) score, higher CD4 count, and lower viral load (p0.05).This statistical procedure permitted for the first time to identify single treatment-naïve HIV individuals having abnormal EEG activity.This procedure might enrich the detection and monitoring of effects of HIV on brain function in single treatment-naïve HIV individuals.

The “chronicization” of HIV infection brings about a growing necessity to attentively evaluate current and potential complications when prescribing the individual therapeutic regimen. Starting from this need, we developed two HIV-comorbidity simulators that, basing on the evidence available in medical literature and starting from the current clinical and demographic features of the individual patient, project and compare the risks of developing and worsening of nephropathy and osteopathy associated with possible ARV regimens. These simulators are embedded in a desktop, user-friendly software thought to be used by the treating physician during prescription discussion with his/her patients, in order to highlight expected clinical outcomes and healthcare resource consumption that may differ according to the therapeutic strategy selected. In this article we present the sources and methods used in developing the mathematical models, alongside a set of examples and the results of cohort-level validation runs.

Primary perivascular epithelioid cell tumors (PECo- mas) are a variety of rare mesenchymal neoplasm about which very little is known. Due to the small number of cases reported in the literature, there is no consensus about a classi fi cation of this disease that might in fl uence clinical practice and disease management. This article describes a primary PEComa of the bladder in which surgical strategy has been adopted. This strategy has shown good results, showing no local or distant relapse after 2 years of follow-up, without the need of adjuvant therapy. This might be the correct strategy in the treatment of urinary PEComas.

// Daniela Gaglio 1, 2, 6, 8 , Silvia Valtorta 1, 2, 3, 4 , Marilena Ripamonti 1, 2 , Marcella Bonanomi 2 , Chiara Damiani 2 , Sergio Todde 5 , Alfredo Simone Negri 6 , Francesca Sanvito 7 , Fabrizia Mastroianni 2 , Antonella Di Campli 8 , Gabriele Turacchio 8 , Giuseppe Di Grigoli 1, 2, 3 , Sara Belloli 1, 2, 3 , Alberto Luini 8 , Maria Carla Gilardi 1, 2 , Anna Maria Colangelo 2, 9 , Lilia Alberghina 2, 9, * , Rosa Maria Moresco 2, 3, 4, * 1 Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), Segrate, Italy 2 SYSBIO.IT, Centre of Systems Biology, Milano, Italy 3 Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy 4 Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy 5 Tecnomed Foundation of University of Milano-Bicocca, Monza, Italy 6 Department of Agricultural and Environmental Sciences - Production, Landscape, Agroenergy University of Milan, Milan, Italy 7 Mouse Histopathology Unit, Department of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy 8 Institute of Protein Biochemistry, National Research Council, Naples, Italy 9 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy * These authors have contributed equally to this work Correspondence to: Daniela Gaglio, email: daniela.gaglio@ibfm.cnr.it Rosa Maria Moresco, email: moresco.rosamaria@hsr.it Keywords: tumor, metabolic rewiring, PET-imaging, metabolomics-mass-spectrometry, oncogenic-K-ras Received: February 02, 2016 Accepted: June 17, 2016 Published: July 07, 2016 ABSTRACT Oncogenic K-ras is capable to control tumor growth and progression by rewiring cancer metabolism. In vitro NIH-Ras cells convert glucose to lactate and use glutamine to sustain anabolic processes, but their in vivo environmental adaptation and multiple metabolic pathways activation ability is poorly understood. Here, we show that NIH-Ras cancer cells and tumors are able to coordinate nutrient utilization to support aggressive cell proliferation and survival. Using PET imaging and metabolomics-mass spectrometry, we identified the activation of multiple metabolic pathways such as: glycolysis, autophagy recycling mechanism, glutamine and serine/glycine metabolism, both under physiological and under stress conditions. Finally, differential responses between in vitro and in vivo systems emphasize the advantageous and uncontrolled nature of the in vivo environment, which has a pivotal role in controlling the responses to therapy.

The Italian National Healthcare System (NHS) processes data concerning outpatient services at public facilities based exclusively upon the weight of services provided. It is the Ministry of Health which initially determines the types of services that can be provided for each pathology. In Italy today (as we await the publication of the new Essential Care Levels already identified by the Ministry of Health) there are still no medical codes specifically associated with specialist outpatient services for the treatment of skin ulcers. This means that not all patients affected by this pathology who turn to public facilities are traceable. It is different where hospital admission is concerned because data is usually obtained from the discharge forms. Unfortunately, the data obtained is not always a true expression of the prevalence of skin ulcers in the hospital environment. In many cases the prevalence of pressure ulcers is not properly reported. This is because their appearance during hospitalization is an indicator of poor hospital care. The lack of data makes it impossible for our NHS to plan appropriate interventions in this area, both organizationally and economically. Scarce financial resources are allocated for the treatment of skin ulcers and their costs fall almost entirely upon the patients and their families. Furthermore, there are no national care networks dedicated specifically to their treatment.

Background Previous evidence showed abnormal sources of resting-state delta ( Material and methods The rsEEG, clinical, and neuropsychological data were collected in 128 naive HIV subjects with normal cognition or mild cognitive deficits and 60 control (Healthy) subjects. The eLORETA freeware estimated source connectivity by the tool called lagged linear connectivity (LLC). Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Healthy and HIV individuals. Results Posterior interhemispheric and diffuse intrahemispheric LLC solutions in alpha sources were abnormally lower in both HIV subgroups with and without mild cognitive deficits subjects, compared with the Healthy group. Noteworthy, HIV subgroup with cognitive deficits showed greater abnormalities than HIV subgroup with normal cognition. Furthermore, AUROC curves of those alpha LLC solutions exhibited moderate accuracies (>0.7) in the discrimination of control vs. HIV individuals with mild cognitive deficits. Conclusions Naive HIV subjects in quiet wakefulness were characterized by abnormalities in widespread alpha source connectivity, which were greater when related to mild cognitive deficits. Widespread alpha source connectivity may reflect HIV effects on brain and cognitive functions before drug regimens. Future studies may test utility of the present approach to select HIV subjects prone to cognitive decline over time and to track brain functions after neuroprotective anti-HIV drug regimens.

Objective Cortical sources of electroencephalographic (EEG) rhythms were investigated in two sub-populations of naive HIV subjects, grouped based on clinical criteria to receive different combination anti-retroviral therapies (cARTs). These EEG sources were hypothesized to reflect beneficial effects of both regimes. Methods Eyes-closed resting state EEG data were collected in 19 (Group A) and 39 (Group B) naive HIV subjects at baseline (i.e. pre-treatment; T0) and after 5 months of cART (T5). Compared with the Group A, the Group B was characterized by slightly worse serological parameters and higher cardiovascular risk. At T0, mean viral load (VL) and CD4 count were 87,694 copies/ml and 435 cells/μl in the Group A and 187,370 copies/ml and 331 cells/μl in the Group B. The EEG data were also collected in 50 matched control HIV-negative subjects. Cortical EEG sources were assessed by LORETA software. Results Compared to the Control Group, the HIV Groups showed lower alpha (8–12 Hz) source activity at T0 while the Group B also exhibited higher delta source activity. The treatment partially normalized alpha and delta source activity in the Group A and B, respectively, in association with improved VL, CD4, and cognitive functions. Conclusions Different cART regimens induced diverse beneficial effects in delta or alpha source activity in the two naive HIV Groups. Significance These sources might unveil different neurophysiological effects of diverse cART on brain function in naive HIV Groups as a function of clinical status and/or therapeutic compounds.

Candida species are regular commensal in humans, but-especially in immunocompromised patients-they represent opportunistic pathogens giving rise to systemic infection. The aim of the present work was to isolate and characterize for their antifungal profile Candida species from different body sites and to analyze the biofilms produced by C. albicans and C. glabrata isolates. Eighty-one strains of Candida species from 77 patients were identified. Epidemiological study showed that the most isolated species were C. albicans (44), C. glabrata (13) and C. parapsilosis (13) mainly from Hematology, Infectious Diseases, Medicine, Neonatology and Oncology Divisions, the majority of the biological samples were swabs (44) and blood cultures (16). The analysis of the biofilm formation was performed at 24 and 48-hours comparing resistant and susceptible strains of C. albicans to resistant and susceptible strains of C. glabrata. Candida albicans has a greater ability to form biofilm compared to C. glabrata, both in the susceptible and resistant strains reaching maturity after 24 hours with a complex structure composed of blastospores, pseudohyphae, and hyphae embedded in a matrix. On the contrary, C. glabrata biofilm was composed exclusively of blastospores that in the resistant strain, after 24 hours, were organized in a compact multilayer different to the discontinuous structure observed in the susceptible analyzed strains. In conclusion, the increasing of the incidence of Candida species infection together with their emerging drug resistance also related to the biofilm forming capability underline the need to monitor their distribution and susceptibility patterns for improving the surveillance and for a correct management of the infection.

Objective Here we tested the effect of combined antiretroviral therapy (cART) on deviant electroencephalographic (EEG) source activity in treatment-naïve HIV individuals. Methods Resting state eyes-closed EEG data were recorded before and after 5 months of cART in 48 male HIV subjects, who were naïve at the study start. The EEG data were also recorded in 59 age- and sex-matched healthy subjects as a control group. Frequency bands of interest included delta, theta, alpha1, alpha2 and alpha3, based on alpha frequency peak specific to each individual. They also included beta1 (13–20 Hz) and beta2 (20–30 Hz). Low-resolution brain electromagnetic tomography (LORETA) estimated EEG cortical source activity in frontal, central, temporal, parietal, and occipital regions. Results Before the therapy, the HIV group showed greater parietal delta source activity and lower spatially diffuse alpha source activity compared to the control group. Thus, the ratio of parietal delta and alpha3 source activity served as an EEG marker. The z-score showed a statistically deviant EEG marker (EEG +) in 50% of the HIV individuals before therapy (p, Highlights • A statistical z-score tested the effect of antiretroviral therapy on resting state EEG sources in naïve HIV individuals. • Many HIV individuals (50%) had abnormal EEG before the therapy, and > 40% showed its normalization after 5 months of cART. • This procedure might monitor effects of cART on brain function in HIV single individuals.

Background: The course of chronic pancreatitis is often unpredictable and many factors are likely to be involved in the progression of the disease. In physiological condition, pancreatic juice exerts significant antibacterial activity, which is impaired in patients with chronic pancreatitis. Aim: Hypothesizing that Helicobacter pylori could, in these conditions, lead to an ascending infection, we aimed to assess the presence of H. pylori sequences in pancreatic juices of patients with chronic pancreatitis. Methods: 40 patients (mean age 52±3 yr) with alcoholic chronic pancreatitis and H. pylori infection were examined. Pancreatic juices were collected during endoscopic retrograde cholangiopancreatography. Using polymerase chain reaction (PCR) with two primers homologous to a portion of urease-C gene, H. pylori DNA was detected. Gastric biopsies, microscopically positive to H. pylori were used as positive controls. Results: All gastric biopsies produced H. pylori-specific DNA products. Conversely, no H. pylori urease-C gene sequences have been detected in any of the pancreatic juices. Conclusion: Our data suggest that the impaired antibacterial activity of pancreatic juices in patients affected by chronic pancreatitis does not have a permissive role for a superimposingH. pyloriinfection in the pancreas. The possibility that Helicobacter species other than pylori may be involved in a superimposing infection requires further investigation.

Considerable evidence indicates that patients with rheumatoid arthritis (RA) are at greater risk of developing atherosclerosis and cardiovascular disease. Recent studies support the predictive ability of endothelial function measures for subsequent atherosclerotic events. We have investigated the effects of infliximab, a chimeric monoclonal anti-tumor necrosis factor (TNF) antibody, on endothelial vasodilation, measured by brachial ultrasonography and on the levels of inflammatory biomarkers and adhesion molecules in ten consecutive patients with severe long-standing RA, despite methotrexate therapy, during the loading phase of infliximab therapy. Flow-mediated dilation (FMD) in RA patients at baseline was significantly impaired compared with healthy controls (7.71 +/- 2.78% vs 14.91 +/- 6.41%; p = 0.008) and improved significantly after infliximab infusion (12.63 +/- 1.63% vs 7.71 +/- 2.78%; p = 0.005). At baseline, a statistically significant correlation between C-reactive protein levels and FMD was found (r = -0.69, p = 0.026). However, this improvement was transitory, as FMD values returned to baseline values before each infliximab infusion at weeks 2, 6 and 14. There were no significant differences in baseline brachial artery diameter between visits, although at each time, the diameter was increased. According to European League Against Rheumatism response criteria, all ten patients were good responders. No significant differences were observed in intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, vascular endothelial growth factor and E-selectin plasma levels before and after each infusions. This study demonstrates that endothelial dysfunction is a reversible phenomenon in RA. The addition of anti-TNFalpha treatment reduces inflammatory symptoms in patients with severe RA. The improvement of endothelial function during the loading phase of therapy is transitory, suggesting an enhanced and persistent TNF-alpha generation within the arterial wall.

HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress.We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α).sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels.HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress.

Background Liver regeneration is a heterogeneous phenomenon involving the proliferation of different cell lineages in response to injury. Under a strong positive selection pressure bone marrow derived stem cells may be involved in this process, by making a contribution to both parenchymal restoration and endothelial cell replacement. We investigate bone marrow stem cell migration to the liver in patients undergoing hepatectomy or with acute on chronic liver failure. Methods We enrolled 6 patients submitted to hepatectomy, 6 patients to cholecystectomy and 8 patients with acute decompensation of liver cirrhosis. Mobilization of CD34+ cells was evaluated by cytofluorimetry on peripheral blood samples at different time points; baseline, 1, 3, 7, 15 and 30 days after surgery and at admission, 1, 7 and discharge among patients with acute on chronic liver failure. 10 healthy subjects undergoing blood donation were also enrolled to evaluated the basal value of CD34+ cells. Results White blood cell counts remained in the normal range (4.1–9.8 × 10 9 /L) in all groups throughout the follow-up. In all patients of Groups 1, 2 and 3, circulating CD34+ failed to show statistically significant differences both as the absolute number and as the percentage at any time point compared to healthy controls. Conclusions Bone marrow derived cell mobilization can not be detected after hepatectomy or during an acute decompensation on a cirrhotic liver. Under these circumstances liver regeneration can probably call upon mature hepatocytes and endogenous progenitor cells. The involvement of extrahepatic progenitors if any, is a rare and limited phenomenon.

Background and Aim Tissue homeostasis and turnover require reserve stem proliferating cells. Several studies performed on immunodeficient animals have suggested a degree of plasticity by the hematopoietic stem cell compartment that may represent source for liver regeneration. We sought to explore the hepatic differentiation potential of hematopoietic stem cells from human cord blood, after toxic liver damage induced by allyl-alcohol in immunocompetent rats. Materials and Methods Wistar rats were divided into groups (A) allyl-alcohol intraperitoneal injection with hematopoietic stem cell intraperitoneal infusion at 1 day and sacrifice 3 days later; (B) stem cell injection and sacrifice 3 days later; (C) allyl-alcohol infusion and sacrifice 4 days later; and (D) sacrifice without any treatment. Livers, spleens, and bone marrows were analysed for human stem cells using flow-cytometry; livers were also tested by histology and immunohistochemistry to study the pattern of hepatic regeneration after damage and human stem cell conversion into hepatocyte-like cells, respectively. Results Flow-cytometry revealed selective recruitment of human hematopoietic stem cells by damaged livers (group A) compared with control group B. In addition, liver damage was reduced in animals treated with stem cells. Immunohistochemistry demonstrated that human stem cells could convert hepatic cells. Conclusions Our study demonstrated that hematopoietic stem cells selectively recruited by injured livers can contribute to hepatic regeneration after acute toxic damage in immunocompetent recipients.

Background and aim Molecular adsorbent recycling system (MARS) treatment is able to remove both hydrosoluble and small- and medium-sized lipophilic toxins. MARS plays an important role in modifying liver failure complications, such as hepatorenal syndrome and hepatic encephalopathy. We sought to evaluate the clinical efficacy and safety of a MARS device in a consecutive series of hepatic failure patients. Materials Twenty patients with acute liver failure, transplantation failure, or acute on chronic liver failure fulfilled the inclusion criteria of total bilirubin ≥10 mg/dL and at least one of the following: hepatic encephalopathy (HE) ≥II grade, hepatorenal syndrome (HRS) for chronic patients or total bilirubin ≥5 mg/dL and HE ≥I grade for acute patients. Results MARS was able to reduce cholestatic parameters and improve neurologic status and renal function parameters in all treated patients. We also observed an improvement in the 3-month survival rate compared to the expected outcome in patients with MELD scores between 20 and 29, as well as 30 and 39. Conclusions Based on these results, we confirm the safety and clinical efficacy of MARS treatment, with the best results in patients with MELD score of 20 to 29. Further studies are necessary to confirm whether this treatment is able to modify patient outcomes and prognosis.

Background. Several studies have demonstrated that bone marrow contains a subpopulation of stem cells capable of participating in the hepatic regenerative process, even if some reports indicate quite a low level of liver repopulation by human stem cells in the normal and transiently injured liver. Aims. In order to overcome the low engraftment levels seen in previous models, we tried the direct intraperitoneal administration of human cord blood stem cells, using a model of hepatic damage induced by allyl alcohol in NOD/SCID mice. Methods. We designed a protocol based on stem cell infusion following liver damage in the absence of irradiation. Flow cytometry, histology, immunohistochemistry and RT-PCR for human hepatic markers were performed to monitor human cell engraftment. Results. Human stem cells were able to transdifferentiate into hepatocytes, to improve liver regeneration after damage and to reduce the mortality rate both in both protocols, even if with qualitative and quantitative differences in the transdifferentiation process. Conclusions. We demonstrated for the first time that the intraperitoneal administration of stem cells can guarantee a rapid liver engraftment. Moreover, the new protocol based on stem cell infusion following liver damage in the absence of irradiation may represent a step forward for the clinical application of stem cell transplantation.

Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million fatalities occurring annually worldwide. Multiple risk factors are associated with HCC disease etiology, the highest incidence being in patients with chronic hepatitis B virus and hepatitis C virus, although other factors such as genetic makeup and environmental exposure are involved. Multiple genetic alterations including the activation of oncogenes and inactivation of tumor suppressor genes are required for malignancy in human cancers and are correlated with increased stages of carcinogenesis and further tumor progression. In this study of 21 HCC patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF), p27(KIP1), and proliferating cell nuclear antigen as potential HCC molecular biomarkers. In our sample set, we found that p27(KIP1) was absent. Univariate survival analysis showed that proliferating cell nuclear antigen expression (diffuse staining >50% of positive cells in tumor) was confirmed as a significant HCC prognostic biomarker for determining patient survival agreeing with previous studies (P = 0.0126, log-rank test). Lower pRb2/p130 expression was associated to a borderline P value of inverse correlation with tumor malignancy and to a positive correlation with respect to the time from HCC diagnosis (Spearman coefficient = 0.568; P < 0.05). Conversely, higher VEGF expression was associated with a poor survival (P = 0.0257, log-rank test). We demonstrate for the first time that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (P < 0.05) in p27(KIP1)-negative HCC patients. pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Furthermore, we have evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a p27(KIP1)-independent manner. Additional studies with larger numbers of patient data would allow the use of multivariable techniques and would be able to further identify patients with poorer survival.

Flow rate measurements in clinical studies require an amount of voided urine greater than 125 to 150 mL. Often patients do not void sufficient amounts of urine, and having them produce repeated flows is often difficult. Transabdominal sonographic scanning of the bladder is a simple method for estimating bladder volume. We determined by sonography the prevoiding bladder volume needed to void a sufficient amount of urine.Sixty-seven patients with a mean age +/- SD of 67.5 +/- 8.0 years underwent free flow rate measurement. Bladder volume was measured by transabdominal sonography when the patient had the sensation to void and after uroflowmetry to calculate residual urine.The voided volume was 220 +/- 127 mL; the postvoiding residual urine volume was 92 +/- 88 mL; and the bladder scan volume was 309 +/- 158 mL. Among all patients, 23.9% had insufficient voided volumes of less than 125 mL in the flow rate measurements, and 31.3% had voided volumes of less than 150 mL. There was a strong correlation between the prevoiding measured volume and the voided volume (r = 0.836; P.0001). Linear regression analysis of the flow rate recording yielded the following formula: voided volume = 11,766 + (0.673 x prevoiding volume).Bladder scanning before uroflowmetry is a useful test for reducing the amount of nonevaluable flow rate data. If a voided volume of greater than 125 mL (150 mL) is required, the mandatory prevoiding bladder scan volume should be greater than 200 mL (250 mL), which would decrease the number of noneligible flow rate recordings from 23.9% to 4.5% (31.3% to 4.5%).

Objective The early phase after liver transplant is considered the period of greatest risk for graft failure. In recent years breath tests have been proposed as a noninvasive method to assess liver function. In particular, the aminopyrine breath test is useful for evaluating the liver viable mass, and the methionine breath test could be used to evaluate oxidative capacity of liver mitochondria. We aimed to perform these tests in the early phase following liver transplant in order to correlate the time course of these tests to the outcome of transplantation. Methods Twenty-three patients undergoing liver transplant were enrolled. The methionine and aminopyrine breath tests were performed on the days 1, 3 and 5, and 2, 4 and 6, respectively, after transplant. Results were expressed as the percentage of administered 13C recovered per hour and as the cumulative percentage of the 13C dose recovered over the test period. Results All but two transplants were successful in the short term and the cumulative percentage of the dose of 13C progressively increased after transplantation, reaching values not significantly different from controls (methionine at day 5). In two patients, primary non-function occurred: in these patients the cumulative percentage of the 13C dose did not increase after orthotopic liver transplant and the results of both breath tests indicated that it always remained significantly lower compared to that of other patients. Conclusions A combination of breath tests, exploring both mitochondrial and microsomal function, could be useful in the early phase after liver transplant in order to evaluate the graft outcome. Eur J Gastroenterol Hepatol 15: 727-732 © 2003 Lippincott Williams & Wilkins

Summary Background : The possibility of inducing oral desensitization in patients with food allergy is still controversial and no standardized programmes are yet available. Aim : To evaluate the safety and efficacy of oral desensitization in patients with allergy induced by the most common food allergens. Methods : Fifty-nine patients with food allergy underwent an oral desensitizing treatment according to standardized protocols. The control group consisted of age- and sex-matched subjects, who followed a strict elimination diet. Specific immunoglobulin E and immunoglobulin G4 were assessed at baseline and after 6, 12 and 18 months. Results : The majority of patients (83.3%) successfully completed the treatment. During treatment, 51.1% of subjects experienced some mild side-effects, easily controlled by the oral administration of antihistamines or sodium cromolyn. Specific immunoglobulin E showed a significant decrease, whilst specific immunoglobulin G4 showed a significant increase in all patients. Conclusions : The immunological findings induced by oral desensitization in food allergy allow us to hypothesize that oral tolerance may be mediated by the same mechanisms as those involved in traditional desensitizing treatments for respiratory allergies. Moreover, the proposed standardized oral desensitization protocols may represent an effective alternative approach in the management of food-allergic patients.

Ethanol is known to have a deleterious effect on liver ischemia–reperfusion injury, but recent reports suggest that light ethanol consumption may produce a protective effect in several organs. We aimed to investigate effects of different doses of ethanol on liver oxidative injury. Rats were fed with ethanol-containing diets (24, 30, 36, 40% for groups A, B, C, D, respectively). After four weeks, livers were exposed to ischemia–reperfusion. Chemiluminescence was recorded; total lipids, adenosine triphosphate, malondialdehyde, reduced glutathione and lactic dehydrogenase were assessed. In all groups, ischemia resulted in the disappearance of O2 •-, a decrease in glutathione and adenosine triphosphate, and stable malondialdehyde values. During the reperfusion phase, O2 •- production, malondialdehyde and lactic dehydrogenase increased, reaching significantly higher values in groups C and D and significantly lower values in group B. The effect of ethanol on ischemia–reperfusion injury seems to be a dose-related response, with an additional toxic effect only at high doses of ethanol.

An experimental murine model was studied to evaluate the orogastrointestinal colonization of Helicobacter pylori and the animal-to-animal transmission. Balb/C mice were infected with H. pylori and housed with uninoculated mice in cages with and without a grate on the floor. Mice were killed after 7, 14, 30, and 45 days, and samples from the esophagus, stomach, small intestine, colon, and rectum were analyzed for H. pylori by PCR and immunohistochemistry and for histological changes. Bacterial colonization was assessed also by culture from stomach samples. H. pylori was cultured by stomach samples of infected mice at 7, 14, and 30 days. Using PCR and immunohistochemistry, H. pylori was detected in inoculated and uninoculated mice in all areas examined, with an high percentage of positive samples in the esophagus and stomach. Moreover transmission was detected, without differences, regardless of whether mice were housed with or without a grate on the floor, supporting an orooral animal transmission.

Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdheyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldheide and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation.

High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory responses and tissue repair. In this study, it was examined whether HMGB1 plays a role in skin wound repair both in normoglycemic and diabetic mice. HMGB1 was detected in the nucleus of skin cells, and accumulated in the cytoplasm of epidermal cells in the wounded skin. Diabetic human and mouse skin showed more reduced HMGB1 levels than their normoglycemic counterparts. Topical application of HMGB1 to the wounds of diabetic mice enhanced arteriole density, granulation tissue deposition, and accelerated wound healing. In contrast, HMGB1 had no effect in normoglycemic mouse skin wounds, where endogenous HMGB1 levels may be adequate for optimal wound closure. Accordingly, inhibition of endogenous HMGB1 impaired wound healing in normal mice but had no effect in diabetic mice. Finally, HMGB1 had a chemotactic effect on skin fibroblasts and keratinoyctes in vitro. In conclusion, lower HMGB1 levels in diabetic skin may play an important role in impaired wound healing and this defect may be overcome by the topical application of HMGB1. © 2008 The Society for Investigative Dermatology.

Objective: We tested the hypothesis that 5 months of combined anti-retroviral therapy (cART) affect cortical sources of resting state cortical electroencephalographic (EEG) rhythms in naive HIV subjects. Methods: Eyes-closed resting state EEG data were recorded at baseline (i.e. pre-treatment; T0), T1 (after 4 weeks of cART), T2 (after 8 weeks of cART), and T5 (after 5 months of cART) in 38 naive HIV subjects. EEG data were also recorded in 40 age-matched cognitively normal subjects for control purposes. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Cortical EEG sources were estimated by LORETA software. Results: Compared to the control group, the HIV group at T0 showed greater delta sources and lower widespread alpha sources. cART induced a global improvement of biological (viral load, CD4 count) and EEG (delta, alpha) markers, remarkable even after 4 weeks. Compared to HIV Responders (>100 cells/ll at 5-month follow up), the HIV Mild Responders (

Background: Helicobacter pylori treatment failure may be due to resistance to macrolides and 5-nitroimidazoles. Aim: To test whether a preliminary in vitro susceptibility test of H. pylori to tinidazole and clarithromycin and a consequent specific regimen could improve the eradication rate. Methods: A total of 109 consecutive H. pylori-positive patients with dyspeptic symptoms were included. At endoscopy, biopsy from the antrum was obtained for H. pylori culture and antimicrobial susceptibility testing. Fifty-six patients were treated with omeprazole, tinidazole and clarithromycin for 10 days (group OTC) and 53 patients received therapy on the basis of the susceptibility test (group SUSC). Treatment success was evaluated by the 13C-urea breath test 1 month after the end of therapy. Results: Eight patients dropped out. Overall primary resistance to clarithromycin, tinidazole and both antibiotics was 13%, 33% and 4%, respectively. In group OTC, H. pylori was eradicated in 81% and 75% of patients by per protocol and intention-to-treat analysis, respectively. Per protocol and intention-to-treat eradication rates for group SUSC were 98% and 91% (P

Summary Background : Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease. Aim : To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima–media thickness of the common carotid artery. Methods : Fifty-two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima–media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well-known risk factor for thrombosis, was assessed. Results : Common carotid artery intima–media thickness was significantly higher in inflammatory bowel disease patients (0.63 ± 0.15 mm) compared with controls (0.53 ± 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima–media thickness with homocysteine levels and age. Conclusions : Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima–media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.

Helicobacter pylori, the most important cause ofgastritis and peptic ulcer, recently has been associatedwith several extradigestive diseases. The aim of thisstudy was to assess the prevalence of Helicobacter pylori infection and the effects of bacteriumeradication in 42 consecutive patients affected byidiopathic chronic urticaria. Helicobacter pylori wasassessed by [13C]urea breath test.Amoxicillin, clarithromycin, and lansoprazole were given to infectedpatients for seven days. Urticaria and gastrointestinalsymptoms were assessed on enrollment and aftereradication. Fifty-five percent of patients proved to beinfected by Helicobacter pylori. Prevalence ofgastrointestinal symptoms did not differ betweeninfected and uninfected patients. Eighty-eight percentof infected patients in whom the bacterium waseradicated after therapy showed a total or partial remission ofurticaria symptoms. Conversely, symptoms remainedunchanged in all uninfected patients. In conclusion,Helicobacter pylori affects a high percentage ofpatients with idiopathic chronic urticaria; however,typical gastrointestinal symptoms do not identifyinfection status. Bacterium eradication is associatedwith a remission of urticaria symptoms, suggesting apossible role of Helicobacter pylori in the pathogenesisof this skin disorder.

Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.

highlights Resting-state EEG rhythms show peculiar frequency/spatial features in naive human subjects with human immunodeficiency virus (HIV). Topography and frequency of the cortical sources estimated by low-resolution electromagnetic tomog- raphy (LORETA) can distinguish groups of HIV and control subjects. The LORETA approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions. abstract Objective: The aim of the study was to test the hypothesis that cortical sources of resting-state electro- encephalographic (EEG) rhythms show peculiar frequency/spatial features in naive human subjects with human immunodeficiency virus (HIV) compared to healthy control subjects. Methods: Resting-state eyes-closed EEG data were recorded in 18 naive HIV subjects (15 males; mean age 39 years ± 2.0 standard error of mean, SEM) and in 18 age-matched cognitively normal subjects (15 males; 38.7 years ± 2.2 SEM). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-12 Hz), beta1 (13-20 Hz) and beta2 (20-30 Hz). Cortical EEG sources were estimated by normalised, low-resolution electromagnetic tomography (LORETA). Results: Mini Mental State Evaluation (MMSE) score was lower in HIV (26.5 ± 0.7 SEM) than in healthy (29.2 ± 0.5 SEM) subjects (p < 0.05). Central and parietal delta sources showed higher amplitude in the HIV than in control subjects. Furthermore, topographically widespread, cortical sources of resting-state alpha rhythms were lower in amplitude in HIV subjects than in control subjects. Conclusions: The present results suggest that topography and frequency of the cortical sources of resting- state EEG rhythms can distinguish groups of HIV and control subjects. Significance: These results encourage future studies in an enlarged cohort of HIV subjects to test the hypothesis that the present methodological approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions.

INTRODUCTION Laparoscopy plays an essential role in the diagnosis of hepatic diseases. During the past few years, minilaparoscopy (ML) has increasingly emerged as an alternative diagnostic method in this field. We hereby present the preliminary results of a randomized trial comparing ML with conventional laparoscopy (CL). PATIENTS AND METHODS 92 with suspected hepatic disease were randomized either to undergo CL (n = 47) or ML (n = 45). For CL, we used a Hopkins-laparoscope (O 11 mm, Storz, Tuttlingen) and ML was performed with a 1.9 mm small-diameter optic (Wolf, Knittlingen). RESULTS Laparoscopy with simultaneous liver biopsy could successfully be performed in 88/92 patients. ML could be performed in a significantly shorter time than CL (25 vs. 28 min, p < 0.05). Liver cirrhosis was diagnosed by laparoscopy in a similar proportion of patients (70% in CL, 56% in ML). In 76% of cases, histology confirmed macroscopic signs of liver cirrhosis. Cirrhosis was found in one patient of each group solely by histologic examination of biopsy specimens. The number of bleeding complications during CL equaled the proportion of hemorrhagias in the ML-group. DISCUSSION In the workup of hepatic disease, ML is a diagnostic tool comparable with CL. The fact that ML can be performed in significantly shorter time and seems subjectively less invasive might be an argument for a better acceptance by patients.

Treatment of chronic leg ulcers remains a major health care issue. Although many reports have examined different topical dressings, none have specifically looked at microcrystalline cellulose (MCC). We aimed to evaluate in a prospective, open study the safety and performance of a MCC membrane (Veloderm) in a series of chronic leg wounds of different aetiology. Fifty-five patients participated in this study. The membrane was applied every 5-10 days for 1 month, immediately after surgical debridement. The wound bed was assessed on days 7, 15 and 30 for erythema, pain, exudate level and infection. The wound size change at 30 days was the primary efficacy parameter and any adverse events were collected and analysed. A wound size change of 55% was achieved at the end of follow-up, with an improvement in all the collected parameters, but the erythema, which showed a mild increase. To date, this is the largest experience with a MCC product in chronic wounds. Our study suggests that this treatment may be safe and useful and deserves further investigation.

Objective The development of atherosclerotic lesions associates with the proliferation of vascular smooth muscle cells (VSMC), and their migration from arterial tunica media to the intima. Fibroblast growth factor (FGF)-2 can trigger either phenomena, which are accompanied by the functional impairment of the p53 transcription factor. However, FGF-2 impact on p53 function in VSMC is largely unknown. Methods and results RT-PCR and Western blot analyses assayed FGF-2 effect on human primary VSMC expression of p53-induced molecules with a role in atherogenesis. Confocal microscopy evaluated whether FGF-2 could affect p53 distribution inside VSMC. Results indicate that VSMC exposure to FGF-2 at amounts stimulating the proliferation and migration of these cells promotes p53 phosphorylation and transient accumulation in VSMC nuclei. This is followed by an increase in the expression of the p53-induced thrombospondin (TSP)-1, a VSMC growth and motility factor, and human double minute 2 (HDM2), an antagonist of p53 transcriptional and growth suppressive activity. At later time points, in agreement with the increase of HDM2 and with the capability of this protein to export nuclear p53 to the cytoplasm, the content of p53 in VSMC nuclei is reduced, and the expression of the p53-targeted TSP-l and HDM2 is diminished. Conclusions Since FGF-2, p53, TSP-1, and HDM2 are expressed in human atherosclerotic lesions, the in vitro effects of FGF-2 described herein may be operative in vivo, providing a molecular mechanism for FGF-2 pro-atherogenic activity.

Background/aim We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. Methods Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy + granulocyte-colony stimulating factor (5 μg/kg/day for 6 days) and standard therapy + granulocyte-colony stimulating factor (15 μg/kg/day s.c. for 6 days). Data on CD34 + cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. Results CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. Conclusions Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation.

Background and aim. The clearance of plasma cytokines by means of albumin dialysis (MARS) has been demonstrated in various studies involving patients affected by either acute liver failure (ALF) or acute on chronic liver failure. The aim of the study was to measure the plasma levels of TNF-a, IL-6, and IL-1β in patients with ALF after each MARS treatment to evaluate the relationship between variations in cytokines levels and patient prognosis. Materials and methods. Ten patients with ALF undergoing several MARS treatments were enrolled (group 1). Blood samples were collected before and after each MARS treatment to measure TNF-a, IL-6, and IL-1β, and other hematochemical parameters. We also enrolled 10 patients with ALF who underwent standard therapy (group 2) as well as a control group of 10 healthy subjects matched for sex and age (group 3). Results. MARS reduced total bilirubin levels, biliary acids, BUN, ammonia, TNF-a, IL-6, and IL-lp (P

Background and aim. Oxidative injury occurs as a direct result of hepatitis C virus (HCV) core protein expression both in vitro and in vivo, and may be due to a direct effect on mitochondria. The ketoisocaproic acid (KICA) breath test is a simple, reliable, and noninvasive test to evaluate hepatic mitochondrial function. Albumin dialysis (MARS) is an effective bridge treatment for patients with acute failure superimposed on chronic liver disease. The aim of our study was to evaluate the improvement of mitochondrial function measured by KICA in patients undergoing MARS for acute-on-chronic HCV liver failure. Materials and methods. Five patients with HCV chronic infection undergoing MARS treatment for acute decompensation were enrolled. Before and after each MARS treatment, patients underwent blood testing for the main hematochemical parameters as well as for mitochondrial function by the KICA breath test and the arterial ketone bodies ratio (AKBR). Results. MARS treatment effectively decreased the serum level of total bilirubin, bile acids, urea, and ammonium. Moreover, MARS treatment produced an increase in AKBR and in the cumulative percentage of 13 CO 2 recovered in exhaled air 2 hours after KICA ingestion. Conclusion. Liver mitochondrial function appears to be beneficially affected by MARS treatment.

Helicobacter pylori infection has been indicated as the main pathogenic factor in the development of chronic gastritis, peptic ulcer disease, and gastric malignancies. Although the vast majority of infected subjects do not carry but a mild, asymptomatic gastritis, still there are some cases in which the eradication of the infection appears mandatory. This review addresses current anti-Helicobacter regimens and pharmacological resources, and highlights the pros and cons of each of them, according to the most recent and reliable clinical trials. Also, basic recommendations are given, regarding treatment choice in the event of the failure of a first or second line eradicating strategy, and about the implementation of standard regimens with newer antibacterial devices as probiotics.

Among the different approaches for diabetes mellitus-pancreas and pancreatic islet transplantation-the use of stem cells represent a renewable alternative source of insulin-producing cells. Stem cells capable of differentiating into beta-like cells can be isolated namely from embryonic cells, bone marrow, and umbilical cord blood, but also from adult organs such as pancreas, liver, and spleen. Several studies have demonstrated that by manipulating culture conditions and using growth and transcription factors of beta-cell lineage (in particular pdx-1 and pax4), embryonic stem cells can differentiate in vitro after formation of embryoid bodies. Bone marrow stem cells can give rise to mesenchymal; endodermal-, and ectodermal-derived cells. In vivo it has been shown that after bone marrow transplantation, using a murine sex-mismatched model, insulin-producing cells expressing the Y chromosome can be detected in the donor pancreas, although not in a significantly number. Cells characterized by a group of markers (Nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) important for beta-cell differentiation have been detected in umbilical cord blood. The recent evidence of the possibility to transdifferentiate stem cells to beta cells encourages further studies in animal models to exhaustively determine the differentiation pathways of stem cells to insulin producing cells. These findings might open the way to a successful human investigation.