A helium-burning white dwarf binary as a supersoft X-ray source.

Type Ia supernovae are cosmic distance indicators1,2, and the main source of iron in the Universe3,4, but their formation paths are still debated. Several dozen supersoft X-ray sources, in which a white dwarf accretes hydrogen-rich matter from a non-degenerate donor star, have been observed5 and suggested as Type Ia supernovae progenitors6-9. However, observational evidence for hydrogen, which is expected to be stripped off the donor star during the supernova explosion10, is lacking. Helium-accreting white dwarfs, which would circumvent this problem, have been predicted for more than 30 years (refs. 7,11,12), including their appearance as supersoft X-ray sources, but have so far escaped detection. Here we report a supersoft X-ray source with an accretion disk whose optical spectrum is completely dominated by helium, suggesting that the donor star is hydrogen-free. We interpret the luminous and supersoft X-rays as resulting from helium burning near the surface of the accreting white dwarf. The properties of our system provide evidence for extended pathways towards Chandrasekhar-mass explosions based on helium accretion, in particular for stable burning in white dwarfs at lower accretion rates than expected so far. This may allow us to recover the population of the sub-energetic so-called Type Iax supernovae, up to 30% of all Type Ia supernovae13, within this scenario.

Statins and aspirin in the prevention of cardiovascular disease among HIV-positive patients between controversies and unmet needs: review of the literature and suggestions for a friendly use.

BACKGROUND: As in non-infected subjects, statins and aspirin have a pivotal preventive role in reducing the cardiovascular related morbidity and mortality in HIV infected patients. The persistence of immune activation in these subjects, could contribute to accelerate atherosclerosis, therefore, these treatments that reduce inflammation could provide additional cardiovascular protection. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. Aim of the present position paper is to provide recommendations aimed to overcome the actual differences and limitations among the current ones and to adapt them to the needs of HIV infected patients. RESULTS: We propose to adopt the new ACC/AHA guidelines, simple to use and cost effective, to use the ASCVD score that seems to estimate more accurately the cardiovascular risk among these patients. We suggest to start statin therapy in all patients with a calculated 10-year risk of a cardiovascular event of 10% or greater. Rosuvastatin and atorvastatin should be preferred. LDL-C target may be adopted. Aspirin should be always associated with a statin, in secondary prevention, while in primary prevention it should be reserved only to patients with ≥ 20% 10-year risk particularly adherent to treatments, and with low risk of bleeding. We suggest to start with a dose of 100 mg/day. Finally, management of antiplatelet agents or novel oral anticoagulants may include selecting antiretrovirals with a lower potential for drug interactions or choosing agents least likely to interact with antiretrovirals. CONCLUSIONS: As demonstrated in surveys, HIV physicians are generally highly committed regarding CVD and autonomous in prescribing statins and ASA. Consequently, in the light of the previously discussed discrepancies among the different guidelines and of the incomplete indications regarding HIV-positive persons, the present suggestions could overcome the actual differences and limitations among the current ones.

Is psychiatric residential facility discharge possible and predictable? A multivariate analytical approach applied to a prospective study in Italy.

BACKGROUND: A growing number of severely ill patients require long-term care in non-hospital residential facilities (RFs). Despite the magnitude of this development, longitudinal studies surveying fairly large resident samples and yielding important information on this population have been very few. AIMS: The aims of the study were (1) to describe the socio-demographic, clinical, and treatment-related characteristics of RF patients during an index period in 2010; (2) to identify predictors and characteristics associated with discharge at the 1-year follow-up; (3) to evaluate clinicians' predictions about each patient's likelihood of home discharge (HD). METHODS: A prospective observational cohort study was conducted involving all patients staying in 23 medium-long-term RFs of the St John of God Order with a primary psychiatric diagnosis. A comprehensive set of socio-demographic, clinical, and treatment-related information was gathered and standardized assessments (BPRS, HONOS, PSP, PHI, SLOF, RBANS) were administered to each participant. Logistic regression analyses were run to identify independent discharge predictors. RESULTS: The study involved 403 patients (66.7% male), with a mean age of 49 years (SD = 10). The participants' average illness duration was 23 years; median value for length of stay in the RF was 2.2 years. The most frequent diagnosis was schizophrenia (67.5%). 104 (25.8%) were discharged: 13.6% to home, 8.2% to other RFs, 2.2% to supported housing, and 1.5% to prison. Clinicians' predictions about HD were generally erroneous. CONCLUSIONS: Very few patients were discharged to independent accommodations after 1 year. The main variables associated with a higher HD likelihood were: illness duration of <15 years and effective social support during the previous year. Lower severity of psychopathology and higher working skill levels were also associated with a significantly greater HD likelihood.

Plasmodium falciparum malaria and Parvovirus B19; a case of acute co-infection.

BACKGROUND: Co-infection with Plasmodium falciparum malaria and Parvovirus B19 in adults is an extremely rare occurrence and, apparently, only one case has been previously reported. Herein we describe a case of acute co-infection with severe anemia and renal failure. CASE PRESENTATION: The patient was a 34-year-old African man presenting myalgia, fatigue, headache, anemia and hepatosplenomegaly. A thin peripheral smear showed Plasmodium falciparum trophozoites and the patient was treated with oral mefloquine. After an initial amelioration, fever, fatigue and myalgia reappeared, the anemia worsened and there was evidence of acute renal failure. No malarial parasites were found with a blood smear. A bone marrow aspiration showed marked erythroid hypoplasia. Parvovirus B19-specific IgM and IgG and viremia were positive. The patient was treated with steroids and blood cell transfusions. After ten days, anemia and renal failure progressively decreased. When last seen, the patient was asymptomatic and the blood values were within the normal range. CONCLUSIONS: The diagnosis of Parvovirus B19 acute infection should be considered in any case of persistent severe anemia and/or renal failure, even in clinical conditions that are well-known causes of anemia and renal failure, such as malaria.

Relations between cardiovascular risk estimates and subclinical atherosclerosis in naive HIV patients: results from the HERMES study.

The aim of the study was to evaluate the cardiovascular risk factors associated with subclinical carotid atherosclerosis in antiretroviral therapy-naïve HIV-infected patients. The HERMES (HIV Exposure and Risk of Metabolic Syndrome) study enrolled therapy-naïve patients attending hospitals in the Italian coordination group for the study of allergies and HIV infection (CISAI [Coordinamento Italiano per lo Studio Allergia e Infezione da HIV]) in 2007. It was designed to identify metabolic syndrome (MS) and cardiovascular risk factors. The present analysis is a nested cross-sectional study with a subset of patients examined by carotid ultrasonography. Consecutive antiretroviral therapy-naïve HIV patients attending the facilities involved in the CISAI were included. Their 10-year probability of cardiovascular events was calculated using the Framingham Risk Score (FRS) and three other cardiovascular algorithms (the Global Framingham Risk Score - GFRS, 'Progetto Cuore' and 'SCORE'). Vascular age was estimated using a new model derived from GFRS and was compared with chronological age. The diagnosis of MS was based on the National Cholesterol Education Programme and International Diabetes Federation (IDF) definitions. Subclinical atherosclerosis was determined as ultrasound carotid intima-media thickness >0.9 mm. Out of 140 patients enrolled in the HERMES study by the four centres participating in the nested study, a total of 72 (51.4%) subjects, with no overt cardiovascular disease, were examined using carotid ultrasonography. The median age was 40 years, 79.2% men. The vascular age was 7.6 years higher than the chronological age. The factors associated with subclinical atherosclerosis were age (P < 0.0001), vascular age (P = 0.0002), body mass index (P = 0.003), waist circumference (P = 0.0002), MS (IDF definition, P = 0.004) and all the cardiovascular (CV) models (FRS, P = 0.01, GFRS, P = 0.002, Progetto Cuore, P = 0.018, SCORE, P = 0.03). Independent of other significant factors, waist circumference was significantly associated with pathological results (P = 0.007). The GFRS (area under the receiver-operating characteristic curves, 0.78; P < 0.001) had slightly better predictive accuracy than the other three CV models (FRS, areas under the curve [AUC] = 0.71, P = 0.003; Progetto Cuore, AUC = 0.74, P = 0.0005; SCORE, AUC = 0.77, P < 0.0001); 55% of patients at intermediate risk (6-20%) had subclinical carotid lesions. Subclinical carotid lesions had a highly significant direct association with all the CV risk predictors. The GFRS and vascular age were highly predictive. We recommend a carotid ultrasonographic examination at least among HIV patients with GFRS > or =6% or with an elevated waist circumference.

Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients.

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.

Surgical site infections in HIV-infected patients: results from an Italian prospective multicenter observational study.

BACKGROUND: The quality of life of the HIV-infected population in developed countries has substantially improved over the years. Accordingly, the clinical limitations in the surgical treatment of the HIV-infected patients are becoming fewer, and the number of HIV-infected patients undergoing surgical interventions of all types is increasing. However, available data on the incidence and risk factors for post-surgical complications, such as surgical site infections (SSI), in HIV-infected patients are still limited and often controversial. The aim of this study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients. METHODS: A 1-year observational prospective multicenter surveillance study was conducted in 11 Italian Infectious Diseases Clinical Centers from which 305 consecutive HIV-infected patients undergoing different surgical procedures were enrolled. Postdischarge surveillance was conducted within 30 days after surgery. A number of variables were included in a multivariate analysis aimed at assessing potential risk factors for SSI, including body mass index, diabetes, Hepatitis C (HCV) and hepatitis B virus infection, lipodistrophy, HIV viral load, CD4 cell count and white blood cell count, preoperative hospital stay, National Nosocomial Infection Surveillance (NNIS) risk score, and any antimicrobial prophylaxis. RESULTS: SSI occurred in 29 of 305 (9.5%) patients, of which 17 (58.6%) SSI occurred during hospital stay, and 12 (41.4%) occurred during the postdischarge period. The SSI of the 29 patients were classified as superficial (21, 72.4%), deep (four, 13.8%), organ/space (one, 3.4%), and sepsis (three, 10.3%). Nearly 50% of the superficial and 50% of the deep SSI occurred during the postdischarge period. Organ/space infection and sepsis accounted for 13.7% of all SSI and were observed during the in-hospital stay. The multivariate analysis revealed that HCV co-infection was significantly associated to SSI occurrence. Total hospital stay was longer among patients with SSI than among those without SSI (p = 0.041). CONCLUSION: Although 92.5% of our HIV-infected patients presented a NNIS score < or = 1, the SSI rate was twofold higher than that reported in Italian and European studies for the general population, with more severe clinical presentations. This is the first report of an association between HCV-HIV co-infection and SSI occurrence. Additionally, the viro-immunological status of our patients was not related to SSI occurrence, which suggests the need for further research for other potential risk factors that may be implicated in the occurrence of SSI.

Jejunal perforation secondary to metastatic sarcomatoid carcinoma of the lung.

The Authors present the third case of small-bowel perforation of a metastatic sarcomatoid carcinoma of the lung. A 62-year-old man underwent a right upper lobectomy because of a lung tumour infiltrating the posterior thoracic wall. The histology showed pleomorphic subtype of a sarcomatoid carcinoma (pT3 pN0 cM0). The postoperative course was uneventful and thus the patient received 5 000 cGY over five weeks. After 5 months the patient was admitted to the Surgical Department for acute abdomen. At laparotomy an advanced fibrinous, bile-stained peritonitis secondary to a solitary perforation of the jejunum 50 cm distal to the Treitz were observed. The microscopical examination showed that the perforated mass consisted of infiltration of dischoesive malignant giant cells, highly pleomorphic multi and mononucleated. The immunohistochemistry, performed with multiple keratin antibodies, revealed epithelial differentiation of malignant cells, compatible with a metastatic carcinoma, consistent to the lung primary. In conclusion, according with literature, the small-bowel perforation is a rare presentation of a metastatic lung carcinoma, and particularly of a sarcomatoid carcinoma. It should be considered in differential diagnosis of patients with acute abdominal symptoms especially in those with a previous treated lung cancer. The surgeons should be aware of the poor outcome of these patients and choose a palliative treatment.

Myelin-specific T cells carry and release magnetite PGLA-PEG COOH nanoparticles in the mouse central nervous system.

Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA-PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood-brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after in vitro assessment of the viability and functionality of nano-loaded MOG35-55 specific T cells, we transferred cells containing the nano-cargo into naïve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.

Molecular diagnosis of skin relapse in acute lymphoblastic leukemia.

Despite improved survival in childhood acute lymphoblastic leukemia (ALL), its recurrence and the recognition of extramedullary dissemination continue to be crucial issues in the management of affected patients. We report the case of a boy with ALL who presented with two skin nodules during maintenance therapy. As histological examination of the routinely stained sections and the study of the immunophenotype of the skin biopsy were not conclusive, molecular analysis was carried out. By means of the heteroduplex analysis of the amplified T cell receptor (TCR) gene products we assessed the clonality of the skin lymphoid infiltrate and showed the same pattern of TCR gamma recombination of the bone marrow at diagnosis. The patient was treated with allogeneic bone marrow transplantation and survives disease-free after 3 years. Since cutaneous relapse in ALL occurs rarely, molecular analysis can be helpful and conclusive in defining the nature of a skin infiltrate.

Raltegravir-based therapy in a cohort of HIV/HCV co-infected individuals.

The relationship between hepatic tolerance and hepatitis C virus (HCV) co-infection has not been extensively studied in clinical practice. We assessed the efficacy and safety of raltegravir-based therapy in an Italian cohort of HIV/HCV co-infected patients. One hundred and forty patients with HIV/HCV co-infection initiating raltegravir from SCOLTA project (Surveillance Cohort Long-Term Toxicity Antiretrovirals) were examined. Of them, 43 were women, with mean age of 45.4±6.4years; 65 (46%) had undetectable HIV-RNA<50copies/mL and 75 (54%) HIV-RNA≥50copies/mL. According to CDC classification, 49 (35%) were in stage C. Based on Fib4 score at the time of starting raltegravir, patients were classified in class I in 41 cases, class II in 68 and in class III in 31 cases. Globally, the Fib4 score slightly decreased during 24months follow-up, from 2.2 to a value of 1.8. Hepatic adverse events of any grade were observed in 67 patients, of which only 2 cases (3%) had severe liver toxicity (grade 3-4). Only one patient had to discontinue the therapy because of adverse events. According to univariate analysis, being in CDC stage C represented a risk for the development of liver toxicity, with a hazard ratio (HR) of 2.27 (95% CI 1.06-4.84, P=0.033). None of the other variables considered (age, sex, years since detection of HIV and HCV-RNA detectable, years of previous HIV therapy, concomitant therapy with PI or NRTI, CD4+ cell count, Fib4, and transaminases level at baseline) resulted statistically correlated to the outcome. In conclusion, raltegravir-based regimens can be safely used in HCV infected patients; in this study, the hepatic toxicity has been found to be more frequent in patients with an advanced HIV disease (CDC stage C), independently of HIV-RNA suppression at raltegravir initiation.

Premature lesions of the carotid vessels in HIV-1-infected patients treated with protease inhibitors.

OBJECTIVES: To evaluate the presence of premature atherosclerotic lesions of epiaortic vessels in HIV-1-infected protease inhibitor-(PI) treated patients compared with PI-naive patients and healthy individuals. DESIGN: One-hundred and two HIV-1-positive patients, including 55 treated with PI for at least 12 months and 47 either naive or treated with PI-sparing regimens, were subjected to epiaortic vessel ultrasonography. These data were compared with those obtained from 104 healthy individuals. METHODS: Intima characteristics, pulsation and resistance indexes, and minimal, peak and mean speed were evaluated using a colour power doppler. Atherosclerotic plaques were described. Independent risk factors and values for glycaemia, cholesterolaemia and triglyceridaemia were considered. Statistical analysis included the chi-square test, Mantel-Haenszel test, odds ratio and logistic regression analysis. RESULTS: Of the PI-treated patients, 29 out of 55 (52.7%) presented acquired lesions of the vascular wall at ultrasonography, whereas similar lesions were found in seven out of 47 (14.9%) PI-naive patients. Of the 104 healthy individuals, seven cases (6.7%) of intimal medial thickness were noted. A slightly significant correlation was found between carotid lesions and age, male sex and hypercholesterolaemia, whereas cigarette smoking, hypertriglyceridaemia and Centers for Disease Control and Prevention stage significantly increased the risk of vascular lesions (P= 0.022, P= 0.017 and P= 0.079 respectively). However, the highest significance regarded use of PI (P= 0.011). These results were confirmed by logistic regression analysis. CONCLUSIONS: These data demonstrate a higher than expected prevalence of premature carotid lesions in the PI-treated compared with PI-naive patients. If confirmed, a periodic ultrasonographic study of the vascular wall should be included in the follow-up of HIV infected patients.

Diffuse necrotic hepatic lesions due to visceral leishmaniasis in AIDS.

A rare case of an AIDS patient who developed scattered necrotic involvement of the liver caused by Leishmania infantum is described. Of interest, marked splenomegaly, hypergammaglobulinemia and serum anti-Leishmania antibodies were absent and an incomplete response to therapy was observed. Diagnosis of visceral leishmaniasis (VL) was achieved by the demonstration of numerous amastigotes in both hepatocytes and macrophages on liver biopsy. Hepatic necrotic lesions, which when extensive could lead to acute hepatic failure, possibly reflect an atypical manifestation of liver involvement caused by L. infantum and depend on the immunological impairment which characterizes AIDS patients, thus preventing the formation of granulomas. Our observation confirms that VL can manifest atypical aspects in HIV-positive patients depending on the degree of the immunodeficiency. The frequency and severity of this pathology accounts for the need to list VL among AIDS-defining conditions.

Response of severe HIV-associated thrombocytopenia to highly active antiretroviral therapy including protease inhibitors.

OBJECTIVE: To investigate the response of HIV-associated severe thrombocytopenia (STP) to highly active antiretroviral therapy (HAART) including protease-inhibitors. METHODS: In this retrospective study, 15 patients with HIV-associated STP (platelet count < 50 x 10(9)/l mostly antiretroviral experienced (13/15), underwent HAART for at least 6 months (median 21; range 6-41 months) during which the platelet (PLT) count and plasmatic HIV-RNA were monitored. The PLT response was compared to that observed in 19 patients previously treated with zidovudine (AZT) monotherapy. RESULTS: HAART induced a significant increase in the PLT count (chi(2)=10.53, P=0.01) within the third month which was sustained up to the sixth month of therapy. No STP relapse was observed among eight PLT responders followed for longer than 6 months (median 27; range 7-41 months). The PLT increase after HAART was similar to that observed with AZT monotherapy, but a greater number of HAART patients were antiretroviral-experienced. HAART determined a PLT response in 10/13 subjects whose thrombocytopenia had not improved after previous AZT monotherapy. After 6 months of HAART, a complete platelet response occurred more frequently in patients with undetectable plasma HIV-RNA levels (P=0.01). CONCLUSIONS: HAART induces a sustained PLT response in HIV-associated STP, even in antiretroviral-experienced subjects and in those with AZT-resistant thrombocytopenia. An undetectable plasma HIV viraemia induced by HAART is necessary for STP recovery.

Chlamydia trachomatis and Mycobacterium tuberculosis lung infection in an HIV-positive homosexual man.

A 31-year-old homosexual man, who was human immunodeficiency virus (HIV)-positive was admitted for fever and cough. Chest computed tomography (CT) revealed the presence of diffuse interstitial reticular nodulation, and brain nuclear magnetic resonance imaging showed the presence of nodular frontal lesions. Microscopic examination of sputum and other body fluids showed the presence of acid-fast bacilli and culture-only growth Mycobacterium tuberculosis. Serology for respiratory tract pathogens was negative except for Chlamydia. An antibody titer in the immunoglobulin G (IgG) class of 1:64 for Chlamydia pneumoniae and, unexpectedly, an antibody titer of 1:1024 for C. trachomatis were found. The patient was successfully treated with antituberculosis agents, and clarithromycin, for presumptive chlamydial infection.

Lopinavir plasma levels in salvage regimes by a population of highly active antiretroviral therapy-treated HIV-1-positive patients.

Increased lopinavir (LPV) exposure obtained in vivo through combination with low-dose ritonavir may overcome a certain grade of resistance but not all. We sought to analyze LPV variability and possible risk factors. LPV trough plasma concentrations were determined by high-performance liquid chromatography after 1, 4, and 12 weeks from salvage regimens and tested in both univariate and multivariate regression analyses with age, gender, weight, risk factors for HIV acquisition, hepatitis C virus reactivity, hepatitis B surface antigen positivity, baseline aspartate transferase (AST) or alanine transferase (ALT) levels, creatinine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) or tenofovir as concomitant drugs, and NNRTIs administered in the previous regimen. Fifty-six patients were included into the study. Among them, 8 of 56 (14.3%) at week 1, 12 of 56 (21.4%) at week 4, and 9 of 56 (16.1%) at week 12 had suboptimal LPV plasma concentrations, defined as trough concentration less than 4 microg/mL. No correlation was found between LPV trough concentrations and assessed variables. In conclusion, pharmacokinetic variability and low LPV concentrations have been found, supporting the use of therapeutic drug monitoring in those starting this drug.

Drug injection in jugular veins: a new risk factor for vascular diseases in HIV-infected patients? A case report.

The authors describe a rare case of diffused thrombosis of the superficial veins in the whole body and periphlebitis with perivascular abscesses in an human immunodeficiency virus (HIV)-infected drug abuser who was using neck veins to inject cocaine and heroin. In addition the patient presented oral candidiasis, hepatitis C virus infection, bronchopneumonitis, and endocarditis of the tricuspid valve with valvular failure. The conditions of the patient needed repeated vascular catheterizations for therapy administration. Similar pathologies, in HIV-infected patients, highly increase the risk of opportunistic infections, especially in the encephalic territory; in addition the need for vascular catheterizations represents a further risk factor for bacterial infections.