HIV-associated progressive multifocal leukoencephalopathy. Current perspectives

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, caused by the polyomavirus JC and occurring almost exclusively in the context of severe immune depression. AIDS represents the most common predisposing condition for PML development. Antiretroviral treatment has reduced PML incidence in HIV-infected subjects, but the disease remains a severe and life-threatening complication of AIDS, considering thus far the lack of an effective anti-JC virus (JCV) direct-acting antiviral drug. In the last decade, the use of monoclonal antibodies for treating immune-based diseases evidenced new predisposing conditions for PML development, promoting a renewed interest in PML pathogenesis. In this article, we review the current knowledge on JCV epidemiology and AIDS-associated PML incidence, JCV viral cycle, pathogenesis, and the interplay with HIV infection. We give an updated overview of diagnostic and prognostic tools available for PML diagnosis and describe past and current therapeutic approaches, including new strategies for PML cure

Reducing the operational cost of cloud data centers through renewable energy

The success of cloud computing services has led to big computing infrastructures that are complex to manage and very costly to operate. In particular, power supply dominates the operational costs of big infrastructures, and several solutions have to be put in place to alleviate these operational costs and make the whole infrastructure more sustainable. In this paper, we investigate the case of a complex infrastructure composed of data centers (DCs) located in different geographical areas in which renewable energy generators are installed, co-located with the data centers, to reduce the amount of energy that must be purchased by the power grid. Since renewable energy generators are intermittent, the load management strategies of the infrastructure have to be adapted to the intermittent nature of the sources. In particular, we consider EcoMultiCloud, a load management strategy already proposed in the literature for multi-objective load management strategies, and we adapt it to the presence of renewable energy sources. Hence, cost reduction is achieved in the load allocation process, when virtual machines (VMs) are assigned to a data center of the considered infrastructure, by considering both energy cost variations and the presence of renewable energy production. Performance is analyzed for a specific infrastructure composed of four data centers. Results show that, despite being intermittent and highly variable, renewable energy can be effectively exploited in geographical data centers when a smart load allocation strategy is implemented. In addition, the results confirm that EcoMultiCloud is very flexible and is suited to the considered scenario

Load Management with Predictions of Solar Energy Production for Cloud Data Centers

Power supply of big infrastructures is today a tremendous operational cost for providers and the expected growth of Internet traffic and services will lead to a further expansion of the computing and networking infrastructures and this, in its turn, raises also concerns in terms of sustainability. In this context, renewable energy generators can help to both reduce costs and alleviate the concerns of sustainability of big infrastructures. In this paper, we consider the case of Data Centers (DCs) composed of a few sites located in different geographical positions and powered with solar energy. Due to the intermittent nature of solar energy, different time zones and price of electricity in different locations, load management strategies are fundamental. We consider predictions of the solar energy production performed through Artificial Neural Networks and we assess the impact of predictions on load management decisions and, ultimately, on the DC performance

Persistent systemic microbial translocation, inflammation, and intestinal damage during Clostridioides difficile infection

Background. Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI. Methods. Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively. Results. Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values. Conclusions. CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated

Cefiderocol for compassionate use in the treatment of complicated infections caused by extensively and pan-resistant Acinetobacter baumannii

Objective: This study presents real-life experience with cefiderocol used on a compassionate basis for treatment of three patients with severe infections caused by extensively/pan-drug resistant (XDR/PDR) Acinetobacter baumannii (Ab). Methods: Serum bactericidal activity was determined and considered as a surrogate of cefiderocol susceptibility. Results: Clinical improvement and microbiological eradication of A. baumannii were observed in all three patients, who were affected by extremely complex conditions either for type of infection, adverse effect or resistance profile of A. baumannii. Conclusion: Cefiderocol for XDR/PDR-Ab infections might be reconsidered, especially in light of the recent disappointing results of the CREDIBLE-CR study

Defective production of interferon-γ and tumour necrosis factor-α by AIDS mononuclear cells after in vitro exposure to Rhodococcus equi

The production of interferon-γ and tumour necrosis factor-α was evaluated in the peripheral blood mononuclear cells (PBMCs) from healthy donors and AIDS patients after Rhodococcus equi infection in vitro. PBMCs from healthy donors secreted elevated levels of IFN-γ and TNF-α when challenged in vitro with killed R. equi, whereas the release of both cytokines was impaired in supernatant cultures from AIDS patients. We conclude that the failure of IFN-γ generation in AIDS patients in response to R. equi is not antigen-specific but it may reflect the global impairment of T-cell function. In such patients, however, the infection with R. equi, a facultative intracellular pathogen which survives and replicates within macrophages, may be responsible for the impairment in the TNF-α release, possibly enhancing the HIV-induced macrophage dysftmction

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes

Objectives: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027– Clostridium difficile infection (CDI). Methods: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027– CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. Results: Overall, 238 patients with 027+ CDI and 267 with 027– CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549–3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906–5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051–3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281–4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437–9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155–125.000, p 0.007) were associated with recurrence in 027– CDI. Conclusions: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity

Continuity of Care During End of Life: An Evolutionary Concept Analysis

PURPOSE: The purpose of this study was to clarify the concept of continuity of care during the end of life with a focus on the patient’s perspective. METHODS: Rodgers’ method of evolutionary concept analysis was used. The analysis was based on literature published in English in the databases Cumulative Index for Nursing and Allied Health Literature, Medline, and PsycINFO. FINDINGS: Analysis revealed that the continuity at life’s end is a dynamic process that depends on the interaction among patients, families, and providers, and is strictly interwoven with the patient’s time perception. CONCLUSION: This analysis showed the complexities surrounding the patient’s experience of continuity at life’s end. IMPLICATION FOR NURSING: Nurses can benefit from a deeper understanding of the patient’s experience, both theoretically and in practice

Is teicoplanin a complementary treatment option for COVID-19? The question remains

We read with great interest the editorial by Baron et al. suggesting the potential use of teicoplanin as an alternative drug to treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. Indeed, this glycopeptide antibiotic, commonly used to treat Gram-positive bacterial infections, also showed potential complementary antiviral activity against severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, as previously highlighted by Zhou et al.; moreover, influenza A and B viruses and feline infectious peritonitis virus (FIPV) were reported as potential targets of teicoplanin and its chemical derivatives [2], [1], [2], [3]. Recently, additional studies have provided evidence that SARS-CoV-2, similarly to SARS-CoV, is a cathepsin L-dependent virus: in fact, these viruses require a multistep infection process including (i) receptor binding, (ii) change in spike (S) glycoprotein conformation, and finally (iii) cathepsin L proteolysis of the S protein, crucial for virus entry. Teicoplanin was found to specifically inhibit the activity of cathepsin L and potentially to play a critical role in blocking cell entry of the virus [2,6,7]