Early systemic insults following traumatic brain injury: association with biomarker profiles, therapy for intracranial hypertension, and neurological outcomes-an analysis of CENTER-TBI data.

PURPOSE: We analysed the impact of early systemic insults (hypoxemia and hypotension, SIs) on brain injury biomarker profiles, acute care requirements during intensive care unit (ICU) stay, and 6-month outcomes in patients with traumatic brain injury (TBI). METHODS: From patients recruited to the Collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI) study, we documented the prevalence and risk factors for SIs and analysed their effect on the levels of brain injury biomarkers [S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and protein Tau], critical care needs, and 6-month outcomes [Glasgow Outcome Scale Extended (GOSE)]. RESULTS: Among 1695 TBI patients, 24.5% had SIs: 16.1% had hypoxemia, 15.2% had hypotension, and 6.8% had both. Biomarkers differed by SI category, with higher S100B, Tau, UCH-L1, NSE and NfL values in patients with hypotension or both SIs. The ratio of neural to glial injury (quantified as UCH-L1/GFAP and Tau/GFAP ratios) was higher in patients with hypotension than in those with no SIs or hypoxia alone. At 6 months, 380 patients died (22%), and 759 (45%) had GOSE ≤ 4. Patients who experienced at least one SI had higher mortality than those who did not (31.8% vs. 19%, p < 0.001). CONCLUSION: Though less frequent than previously described, SIs in TBI patients are associated with higher release of neuronal than glial injury biomarkers and with increased requirements for ICU therapies aimed at reducing intracranial hypertension. Hypotension or combined SIs are significantly associated with adverse 6-month outcomes. Current criteria for hypotension may lead to higher biomarker levels and more negative outcomes than those for hypoxemia suggesting a need to revisit pressure targets in the prehospital settings.

Switch to SGLT2 Inhibitors and Improved Endothelial Function in Diabetic Patients with Chronic Heart Failure.

PURPOSE: The use of sodium-glucose-cotransporter-type-2 inhibitors (SGLT2i) was associated in previous studies with an improved vascular function in non-human experimental models. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with chronic heart failure (CHF) and type-2 diabetes mellitus (T2DM), switching from other oral hypoglycemic agents to SGLT2i in an observational study. METHODS: Twenty-two consecutive outpatients with CHF and T2DM were enrolled after switching to SGLT2i therapy, and compared with 23 consecutive controls from the same registry comparable for principal clinical characteristics. In all patients, endothelial function was assessed by FMD at baseline and after 3 months of follow-up. RESULTS: Three months of therapy with SGLT2i were associated with a statistically significant improvement in endothelial function (19.0 ± 5.7% vs 8.5 ± 4.1%, p < 0.0001); baseline levels of FMD were comparable between groups (p n.s.). Therapy with SGLT2i was significantly associated to improved FMD levels even at multivariable stepwise regression analysis (p < 0.001). CONCLUSIONS: Switch to SGLT2i in patients with CHF and T2DM was associated in an observational non-randomized study with an improved endothelial function.

A Bibliometric Analysis of 4 Major Foot and Ankle Surgery Journals.

Research publication is a central to the scientific process and comprehensive bibliometric analysis is a leading way to better understand trends within research. Currently, there are limited bibliometric analyses of literature pertaining to foot and ankle surgery. This study aims to quantify the volume of research and investigate what may affect publication and citation. Journals associated with the 3 major orthopedic foot and ankle societies (Foot & Ankle International[FAI], Foot and Ankle Surgery, and The Foot) and one podiatric college (Journal of Foot and Ankle Surgery®) were evaluated from January 2009 to December 2018 using Scopus (Elsevier, Amsterdam, the Netherlands). Descriptive statistics were used to summarize article characteristics and regression modeling was used to determine factors associated with a country's current and future productivity and an article's citation rate. A total of 4994 articles were published over the 10-year period, with the largest contributor of publications being the United States of America (USA), who produced 2096 (41.8%) publications. Regression analysis found no association between a country's productivity and gross domestic product or population. There was no significant relationship between a country's baseline publication rate and future publication rate. The variables significantly associated with an increased citation count were; the number of years since publication, the number of authors, publication in FAI and if the article was a review. To our knowledge this is the largest bibliometric analysis of foot and ankle publications. The majority of research is being produced by the USA, but there are numerous complex factors associated with citation and publication rates. Further research is required to fully assess these factors and characterize the state of foot and ankle surgery research.

Readability of foot and ankle consent forms in Queensland.

BACKGROUND: The aim of this study was to conduct a readability analysis on both patient take-home information and consent forms for common foot and ankle procedures. Our hypothesis was that the objective reading skills required to read and comprehend the documentation currently in use would exceed the recommendations in place by both national and international bodies. METHODS: The current Queensland Health consent forms are divided into specific subsections. The readability of consent form subsections C and G (sections containing detailed information on risks of the procedure and pertaining to informed patient consent specifically) and patient take-home information (provided as take-home leaflet from the consent form which is procedure specific) was assessed by an online readability software program using five validated methods calculated by application of the algorithms for (i) Flesch-Kincaid grade level, (ii) the SMOG (Simple Measure of Gobbledygook), (iii) Coleman-Liau index, (iv) automated readability index and the (v) Linsear Wriste formula. RESULTS: The mean ± standard deviation reading grade level of risk (section C), grade level of patient consent (section G) and grade level for procedure-specific take-home patient information were 8.7 ± 0.9, 11.6 ± 1.2 and 7.5 ± 0.2, respectively. CONCLUSION: The readability of sections C and G of the Queensland Health consent form exceeds the recommendations by national and international bodies, but the patient take-home information appears suitable. Consideration should be given to lower the reading grade level of patient consent forms to better reflect the reading grade of the Australian population.

Switch to direct anticoagulants and improved endothelial function in patients with chronic heart failure and atrial fibrillation.

BACKGROUND: Chronic heart failure (CHF) is characterized by higher rates of atrial fibrillation (AF) and endothelial dysfunction (ED). First line anticoagulant therapy in AF is represented by direct oral anticoagulants (DOACs); several patients, however, are still treated with vitamin-K inhibitors. The use of DOACs is associated in previous studies with an improved vascular function. We therefore sought to evaluate possible changes in endothelial function assessed by flow-mediated dilation (FMD) in patients with CHF and AF shifting from warfarin to DOACs. METHODS: Forty-three consecutive outpatients were enrolled in the study. FMD was assessed at baseline and after 4 months. Patients were compared according to AC therapy. RESULTS: After the first measurement of FMD, 18 patients "switched" to DOACs because of poor compliance to warfarin therapy or time in therapeutic range, 19 patients continued to use DOACs, 6 warfarin. "Switched" patients to DOACs therapy showed an improved FMD (19.0 ± 6.6% vs 3.8 ± 1.3%, p < 0.0001); C-reactive protein (CRP) levels decreased in "switched" patients from 1.4 ± 0.5 to 1.0 ± 0.7 mg/dl (p < 0.05). FMD and CRP changes were not significant in patients who did not changed anticoagulant therapy. In switched patients, changes in CRP levels were proportional to FMD changes (r = -0.50, p < 0.05). Shifting from warfarin to DOACs was significantly correlated to improved FMD levels even at multivariable analysis (p < 0.05). CONCLUSIONS: Switch from warfarin to DOACs in patents with CHF and AF was associated in an observational non randomized study with an improved endothelial function. Changes in FMD values were related to changes in CRP levels.

Clustering in light nuclei and their effects on fusion and pre-equilibrium processes / Agrupamiento de núcleos ligeros y sus efectos en la fusión y procesos de pre-equilibrio

Summary The study of heavy ion nuclear reactionis an important tool to observe and disentangle different and competing mechanisms, which may arise in the different energy regimes. In particular, at relatively low bombarding energy, it is quite interesting the comparison between pre-equilibrium and thermal emission of light charged particles from hot nuclear systems [1-6]. Indeed, the nuclear structure of the interacting partners can be strongly correlated to the dynamics, especially at energies close to the Coulomb barrier, and this effect emerges when some nucleons or clusters of nucleons are either emitted or captured. In particular, a major attention has been devoted, in the last years, to the possible observation of cluster structure effects in the competing nuclear reaction mechanisms, especially when fast processes are involved. At this purpose, the four reactions 16O+30Si at 111 MeV, 16O+30Si at 128 MeV, 18O+28Si at 126 MeV, 19F+27Al at 133 MeV have been measured to study the onset of pre-equilibrium in an energy range where, for central collisions, complete fusion is expected to be the predominant mode. Experimental data were collected using the GARFIELD + RCo array [7], fully equipped with digital electronics at the LegnaroNational Laboratories. The comparison between experimental data and different model predictions have been performed: in particular, both dynamical models based either on Stochastic Mean Field (TWINGO) or Anti-symmetrized Molecular Dynamics and fully statistical models (GEMINI++) have been considered. Simulated events are filtered through a software replica of the apparatus, to take into account all possible distortions of the experimental distributions due to the finite size of the apparatus.

Resumen El estudio de la reacción nuclear iónica pesada es una herramienta importante para observar y esclarecer los diferentes mecanismos que compiten entre sí, que pueden surgir en los diferentes regímenes energéticos. En particular, a una energía de bombardeo relativamente baja, es bastante interesante la comparación entre el preequilibrio y la emisión térmica de partículas ligeras cargadas por sistemas nucleares calientes [1-6]. De hecho, la estructura nuclear del grupo que interactúa puede estar fuertemente correlacionada con la dinámica, especialmente en energías cercanas a la barrera de Coulomb, y este efecto surge cuando se emiten o capturan algunos nucleones o grupos de nucleones. En particular, se ha dedicado una gran atención, en los últimos años, a la posible observación de los efectos de la estructura del agrupamiento en los mecanismos de reacción nuclear competitivos, especialmente cuando se trata de procesos rápidos. Para este propósito, las cuatro reacciones 16O + 30Si a 111 MeV, 16O + 30Si a 128 MeV, 18O + 28Si a 126 MeV, 19F + 27Al a 133 MeV se han medido para estudiar el inicio del preequilibrio en un rango de energía en el cual, para colisiones centrales, se espera que la fusión completa sea el modo predominante. Los datos experimentales se recogieron utilizando la matriz GARFIELD + RCo [7], totalmente equipada con electrónica digital en los Laboratorios Nacionales Legnaro. La comparación entre los datos experimentales y las diferentes predicciones de modelos se han llevado a cabo: en particular, se han considerado los modelos dinámicos basados en el Campo Medio Estocástico (TWINGO) o Dinámica Molecular Antisimétrica y modelos completamente estadísticos (GEMINI ++). Los eventos simulados se filtran a través de una réplica de software del aparato, para tener en cuenta todas las posibles distorsiones de las distribuciones experimentales debido al tamaño finito del aparato.

ODONTOLOGIA DO ESPORTE - UMA PROPOSTA INOVADORA / SPORTS DENTISTRY - AN INNOVATIVE PROPOSAL / ODONTOLOGÍA DEL DEPORTE - UNA PROPUESTA INNOVADORA

RESUMO O objetivo deste trabalho é inserir definitivamente a odontologia no contexto do esporte de alto rendimento, com o firme propósito de estabelecer uma linguagem comum com a medicina do esporte. Consideramos que as práticas clínicas aplicadas a atletas de alto desempenho devem obedecer a regras e momentos adequados, levando-se em conta o contexto das demandas relativas aos atletas de ponta, ou seja, o desgaste fisiológico e o processo adaptativo ao sobre-esforço, e todas as suas consequências. A odontologia dentro dos clubes esportivos promoveria a saúde bucal e sistêmica dos atletas, controlando lesões bucais em integração com outros departamentos da área médica, equilíbrio hídrico, controle dietético, sobretreinamento e uso de energéticos e isotônicos. Quando as ações educativas forem inseridas desde a infância nas práticas esportivas, teremos, certamente, menor número de problemas bucais com mais necessidades preventivas que curativas. Sugerimos para as categorias de base, para atletas em formação, a inclusão de um odontopediatra nos clubes esportivos, como um profissional de importante atuação em saúde.

ABSTRACT The purpose of this work is to definitively insert Dentistry in the context of high performance sports, with the main goal of establishing a common language with Sports Medicine. We consider that the clinical practices applied to high performance athletes should obey appropriate rules and moments, taking into account the context of the demands on the top athletes, i.e., the physiological wastage and the adaptive process to over-effort, and all its consequences. Dentistry inside the sports clubs would promote the oral and systemic health of athletes, controlling oral lesions integrated with other medical departments, water balance, dietary control, overtraining, and the intake of energy and isotonic drinks. When educational actions are inserted since childhood in sports practices, we will certainly have fewer oral problems with more preventive than curative needs. We suggest for the basic categories, for athletes in training, the inclusion of a pediatric dentist in sports clubs, as a health professional who plays an important role.

RESUMEN El objetivo de este trabajo es, sin duda introducir la odontología en el contexto del deporte de alto rendimiento, con el firme propósito de establecer un lenguaje común con la medicina deportiva. Creemos que la práctica clínica aplicada a los atletas de alto rendimiento deben obedecer las reglas y los momentos apropiados, teniendo en cuenta el contexto de las demandas relacionadas con atletas de alto rendimiento, es decir, el desgaste fisiológico y el proceso de adaptación a un exceso de ejercicio, y todas sus consecuencias. La odontología, en los clubes deportivos promovería la salud oral y sistémica de los atletas mediante el control de las lesiones orales, interactuando con otros departamentos médicos, el balance hídrico, control de la dieta, el sobreentrenamiento y el consumo de bebidas energéticas e isotónicas. Cuando se introducen actividades educacionales desde la infancia en las prácticas deportivas, sin duda vamos a tener problemas dentales menores, con mayor necesidad de prevención en lugar de curación. Sugerimos a las categorías básicas, para los atletas en formación, incluir un dentista pediátrico en los clubes deportivos, como profesional de importante acción relacionada con la salud.

Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop.

The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as "possible", "optional" or "mandatory" according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the indication to follow either strategy is also based on the stage of liver fibrosis; (d) virological monitoring is modified to include the definitions of failure and of sustained virological response to interferon therapy; (e) the recommendation to use HBV DNA assays with high sensitivity and wide linear ranges is underlined (f) guidelines on post-treatment follow-up after finite treatment with NA, potential side effects of therapy and non-virological monitoring are defined; (g) definitions and treatment of patients without optimal response to NA are reported; (f) treatment and monitoring of compensated or decompensated cirrhosis and hepatocellular carcinoma are updated.

Adefovir dipivoxil resistance patterns in patients with lamivudine-resistant chronic hepatitis B.

BACKGROUND: Lamivudine (3TC)-resistant chronic hepatitis B patients demonstrated a higher rate of adefovir dipivoxil (ADV) resistance compared with nucleoside-naive patients. This study describes ADV mutation patterns in 3TC-resistant patients treated with ADV+3TC or ADV monotherapy, investigating whether mutations selected during 3TC therapy predispose to ADV resistance. Risk factors for ADV resistance were also evaluated. METHODS: A total of 60 3TC-experienced patients were treated with (or switched to) ADV monotherapy (30 patients) or ADV+3TC combination therapy (30 patients), and followed for at least 12 months. In all patients the hepatitis B virus reverse transcriptase (RT) region was amplified and directly sequenced before initiating ADV. The RT sequence was reevaluated for virological breakthrough patients and phenotypic analysis was performed for several patients. RESULTS: In total, 14 (23%) patients showed virological breakthrough (10/30 on ADV monotherapy and 4/30 on ADV+3TC). ADV resistance mutations (rtA181V/T and rtN236T) were detected alone or in combination for 11/14 patients, whereas novel substitutions were present in 3 patients. Before ADV treatment, apart from 3TC resistance signature mutations, additional changes were found, including the rtA181T mutation, which was already present in 2/14 ADV-resistant patients. CONCLUSIONS: Although most patients showed virological breakthrough because of the well known rtA181V/T and rtN236T substitutions, more complex patterns were also found. ADV monotherapy, dose reduction and suboptimal virological response after 48 weeks of therapy were significantly associated with ADV resistance.

B-mode ultrasound study of carotid plaques in HIV-positive patients to detect the presence of inflammatory endothelial lesions.

Several reports have indicated that patients with low CD4+ cell count could be at a higher risk for arterial lesions or cardiovascular disease (CVD). Recently, current use of abacavir has been associated with an excess risk of CVD. High sensitivity-C-reactive protein and interleukin-6 levels were high for patients receiving the drug. These data lead to the hypothesis that alternative mechanisms may be at work other that those linked to lipid changes and "classic" risk factors for atheroma. Consequently, we investigated the ultrasound characteristics of carotid plaques in HIV-positive patients comparing the results with those obtained from patients affected by atherosclerosis and patients with arteritis. The study population included 110 HIV-positive patients and 91 HIV-negative patients (61 atherosclerotic patients and 30 with arteritis). All patients were subjected to ultrasonography of the epi-aortic vessels. When compared to atherosclerotic patients, there was a significantly higher proportion of HIV-positive patients with hypoechogenic and homogeneous lesions, uniform in their parietal and endoluminal portions with a smooth or slightly irregular surface. No significant differences were found between HIV-positive and arteritis patients. This ultrasonographic study confirms that inflammatory mechanisms could play a major role in the onset of vascular damage in HIV-1 positive patients.

Occult HBV infection in hemodialysis setting is marked by presence of isolated antibodies to HBcAg and HCV.

BACKGROUND: Hepatitis B virus (HBV) infections are a matter of concern in hemodialysis units; occult HBV infections (serum HBsAg negative but HBV DNA positive) were demonstrated in this setting, and this involves further concerns regarding possible transmission and pathogenic consequences. This study aimed to investigate the prevalence and correlates of occult HBV infection in a group of patients with reference to a single hemodialysis unit in southeastern Italy. METHODS: We analyzed HBV serology and DNA (using a qualitative nested PCR) in 128 HBsAg-negative hemodialysis patients, and correlated the results obtained, with sex, age, hemodialysis duration and HCV seropositivity. RESULTS: As a whole, occult HBV infection was demonstrated in 34/128 patients (26.6%); HBV DNA detection was more frequent when anti-HBcAg antibodies were detected in isolation (72%) than when associated with anti-HBsAg antibodies (31%). Among HCV-seropositive patients, occult HBV infection was observed in 66%, and among these as many as 14/15 patients (93%) who were HCV+/anti-HBcAg+ had serum HBV DNA detectable. On multivariate analysis, HCV seropositivity and the presence of anti-HBs were still respectively correlated to the presence and absence of occult HBV infection. CONCLUSIONS: Occult HBV infection is frequent among hemodialysis patients in our geographical area, particularly correlated to the presence of isolated anti-HBcAg and anti-HCV antibodies. Thus, the presence of isolated anti-HBcAg should prompt the clinician to evaluate a possible occult HBV infection especially if anti-HCV antibodies are also detectable; this condition, in fact, seems to strongly predict the detection of HBV DNA.

A color Doppler ultrasound-based comparative study between stavudine and non-stavudine regimens in the onset of vascular lesions in HIV-1-positive patients.

BACKGROUND: The present study aimed to investigate the role of stavudine in the onset of premature vascular lesions using an ultrasound color Doppler evaluation of the carotid vessels. PATIENTS AND METHODS: A total of 266 patients were evaluated: 149 were treated with stavudine (group I) and 117 without stavudine (group II). RESULTS: Of the patients in group I, 41% exhibited vascular lesions vs. 26% in group II (p=0.0103). The two groups were further divided into subgroups Ia (stavudine and proteinase inhibitor, PI), Ib (stavudine and non-nucleotidic reverse transcriptase inhibitor, NNRTI), IIa (PI, without stavudine) and IIb (NNRTI without stavudine). A higher prevalence of lesions emerged in group Ia, while group IIa were at higher risk of developing vascular lesions than groups Ib and IIb. CONCLUSION: Although stavudine per se does not seem to determine damage of the epiaortic vessels, the association of a PI with stavudine is related to a significantly higher rate of lesions.

Lack of correlation between serum anti-HBcore detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis.

BACKGROUND: While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated. AIM: To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy. PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically METHODS: proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis. RESULTS: Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0%vs 58.7%, P= 0.03), had lower transaminase levels (3.3 +/- 2.0 vs 3.8 +/- 2.5 u.l.n., P= 0.004), and had higher rate of alcohol intake (38.3%vs 22.5%, P < 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34-2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41-2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69-1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76-1.95). CONCLUSIONS: In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.

Functional impairments of microcirculation in HIV-positive patients: a laser Doppler fluxometry-based investigation.

PURPOSE: The aim of our study was to investigate the morphologic and functional characteristics of microcirculation in HIV-positive patients. Microcirculation was investigated by means of capillaroscopy and laser Doppler fluxometry (LDF). The results were compared with those obtained from healthy subjects and patients affected by sclerodermia. METHOD: We evaluated 140 subjects: 69 HIV-positive, 48 sclerodermic, and 23 healthy individuals. The groups were compared for resting flow (RF), mean flow during cold test, mean flow during the recovery, postocclusive reaction, and time of recovery after reactive hyperaemia. RESULTS: RF (p = .0035), flow during the cold test (p = .008), recovery (p = .03), and postocclusive reaction (p = .007) results were higher in HIV-1 positive patients with respect to the other two groups. Recovery after postocclusive reaction in HIV-positive patients was longer than in healthy individuals. Time from diagnosis and a pathologic electromyography were significantly related to a vasospasm reduction induced by the cold test (p = .022). The recovery was also influenced by the time from disease diagnosis (p = .0016). CONCLUSIONS: HIV patients seem to have an altered microcirculation regulation, with increased perfusion of the capillary territory. This could be related to the length of period of infection and a coexisting neuropathy.

Rapid progression of carotid lesions in HAART-treated HIV-1 patients.

To obtain data on the evolution of carotid lesions, we evaluated 133 patients at their first antiretroviral regimen, followed for at least 2 years; 77 treated with protease inhibitors (PIs): Group A and 56 with non-nucleosidic reverse transcriptase inhibitors (NNRTIs): Group B. All patients were subjected to carotid ultrasonography. In Group A, among the previously normal patients 22.5% developed lesions, 40% remained normal, 37.5% shifted to other antiretroviral regimens. Among the 37 previously pathologic patients, 46% worsened, 19% were stable, in 8% the lesions had disappeared, 27% shifted. In Group B, among the previously normal patients, 12.7% developed lesions, 80.8% remained unaltered, 6.5% shifted. Among the previously pathologic patients, 12.5% worsened, lesions reversed in 25%, remained stable in 50% and 12.5% shifted to PI. At statistical analysis, in Group A both the percentage of patients developing new lesions and the percentage of patients who worsened was significantly higher. In conclusion, we evidenced a more rapid onset of lesions in patients treated with PIs with respect to patients treated with NNRTIs and towards a more rapid evolution of the previous lesions. The shift from PIs to NNRTI/3 NRTI seems related to a lower rate of evolution. Interestingly, a disappearance of lesions was detected in both groups.

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

BACKGROUND: We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. METHODS: The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. RESULTS: The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. CONCLUSION: Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.

Pregnancy and human herpesvirus 8 reactivation in human immunodeficiency virus type 1-infected women.

To investigate the impact of pregnancy on human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus type 1 (HIV-1)-infected women, the HHV-8 DNA presence and load were analyzed in peripheral blood mononuclear cells (PBMCs) and cervicovaginal secretions (CVSs) from 15 pregnant women coinfected with HIV-1 and HHV-8. HHV-8 detection was analyzed in relation to anti-HHV-8 antibodies and HIV-1-related parameters. Nucleotide sequence analysis of an ORFK1 hypervariable region of the HHV-8 strains was performed. HHV-8 was detected in maternal PBMCs (5/15 women) from the second trimester and in CVSs (5/15 women) mainly from the third trimester. The HHV-8 load significantly increased late in pregnancy in both maternal compartments and was associated with a significant increase in HIV-1 shedding in the genital tract. Antilytic antibodies were significantly more common in HHV-8 DNA-positive women. An elevated HHV-8 load was found in the PBMCs of an infant born to a mother with large amounts of HHV-8 in both compartments at delivery. Different ORFK1 subtypes were found in maternal samples, whereas the same subtype was identified in the mother-child pair. These data suggest that pregnancy may induce HHV-8 replication in HIV-1-infected women. An augmented HHV-8 load may, in turn, influence mother-to-child transmission, since one of the HIV-1-infected mothers with HHV-8 reactivation transmitted her ORFK1 subtype to the infant, who showed a high level of HHV-8 viremia indicative of a primary infection. This finding documents for the first time the perinatal transmission of a specific HHV-8 subtype. Vertical transmission may thus play a role in HHV-8 spread also in areas of subendemicity among HIV-1-infected women.

Influence of genotype 3 hepatitis C coinfection on liver enzyme elevation in HIV-1-positive patients after commencement of a new highly active antiretroviral regimen: results from the EPOKA-MASTER Cohort.

BACKGROUND: The independent role of hepatitis C virus (HCV) genotype 3 in liver transaminase elevation following highly active antiretroviral regimens is still controversial. METHODS: Analysis of data from a cohort of 492 HIV/HCV-coinfected patients was conducted using an intention-to-treat approach. Incidence of grade > or = III liver transaminase elevation was estimated per 100 patient-years of follow-up. Univariate and multiple proportional hazards regression analysis of factors that may predict liver enzyme elevation was performed. RESULTS: The incidence of grade > or = III hepatotoxicity was 25 per 100 patient-years among patients coinfected with HCV genotype 3 and 11 per 100 patient-years among those with other genotypes. On multiple proportional hazard regression analysis, time-to-grade > or = III liver enzyme elevation was directly correlated with HCV genotype 3 (hazards ratio [HR]: 2.0, 95% CI: 1.3 to 2.9; P = 0.001), male gender (HR: 2.7; 95% CI: 1.3 to 5.7; P = 0.007), chronic hepatitis B virus infection (HR: 2.9, 95% CI: 1.5 to 5.9; P = 0.002), and alanine aminotransferase level at baseline (per 10 IU/L HR: 1.10; 95% CI: 1.06 to 1.15; P < 0.001). In the same model, higher CD4 T-cell counts at baseline were inversely correlated with risk of hepatotoxicity (HR: 0.998; 95% CI: 0.997 to 0.999; P = 0.036). Moreover, among patients experienced to antiretroviral drugs, previous grade > or = III hepatotoxicity (HR: 2.8; 95% CI: 1.8 to 4.3; P < 0.001) was an adjunctive independent risk factor. CONCLUSIONS: HIV-positive patients coinfected with HCV genotype 3 displayed a higher risk of relevant hepatotoxicity, independently from other clinical variables. The impact of HCV genotype outweighed the role of drugs in determining hepatotoxicity.