Clearance of human papillomavirus related anal condylomas after oral and endorectal multistrain probiotic supplementation in an HIV positive male: A case report.

Abstract Go to: Introduction: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity. Go to: Conclusion: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route

Rapid decline of fasting glucose in HCV diabetic patients treated with direct-acting antiviral agents

Association between HCV infection and diabetes has been widely postulated. Little is known about the impact of direct acting antiviral agents (DAAs) on glycemic control. Aim of our study was to evaluate the glycemic control modifications in a case series of HCV+ diabetic population receiving DAAs. We retrospectively evaluated 149 HCV+ patients in two different institutions affiliated to the Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with T2DM (19% of total population) who were receiving different IFN-free regimens. During-treatment fasting glucose values were available for 21 patients and analysis showed a statistically significant reduction (p=0,007), the reduction mean value was -52,86 mg/dl. An A1C value during treatment (week 4 or week 8 or week 12) was available for 10 patients and the analysis showed a statistically significant reduction (p=0,021) with a reduction mean value of -1,95%. 6 patients (23%) needed to reduce hypoglycemic drugs, 8 of 10 patients showed reduction of A1C, 14 of 21 patients (67%) showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, BMI and HIV status. In order to avoid hypoglycemic events, diabetic patients undergoing DAAs should be closely monitorized for reduction of hypoglycemic drugs. Furthermore, diabetes could be considered, in our opinion, as an element to prioritize treatment in those patients with no apparent liver disease

MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients

Abstract BACKGROUND: Several in vitro studies suggested the microRNA-29 (miRNA-29) family is involved in regulating HIV-1 and modulating the expression of interleukin (IL)-32, an anti-HIV-1 cytokine. METHODS: To investigate the contribution of the miRNA-29 family to HIV-1 infection in vivo, we compared miRNA-29 expression in PBMC collected from 58 HIV-1-infected patients, naïve for antiretroviral therapy, and 21 gender- and age-matched HIV-1 seronegative healthy donors, using RT-Taqman assays. The relation between miRNA-29 levels and HIV-1 viro-immunological markers and the activation rate of antiviral immune response were also evaluated. In addition, we profiled miRNA-29 expression in CD4+ T lymphocytes and CD14+ monocytes collected from 5 antiretroviral treated HIV-1 infected patients. RESULTS: miRNA-29b levels were higher in HIV-1-infected patients than in the control group (p < 0.001). There were no correlations with either HIV-1 RNA levels or CD4+ T count, whereas a significant correlation was found between miRNA-29-a/c levels and integrated HIV-1 DNA (miRNA-29a: p = 0.009, r = -0.448; miRNA-29c: p = 0.029; r = -0.381). When the HIV-1-infected patients were grouped on the basis of their plasma HIV-1 RNA and CD4+ T cell count, we also found that patients expressing the lowest levels of miRNA-29c showed high viraemia, low CD4+ T cell count and high levels of integrated HIV-1 DNA. Moreover, miRNA-29b levels were correlated with those of IL-32nonα (p = 0.028; r = -0.298). Patients expressing higher levels of miRNA-29b showed lower levels of MxA, an interferon-stimulated gene, also induced by IL-32 (p = 0.006 r = -0.397). Lastly, we found that CD4+ T lymphocytes and CD14+ monocytes shared similar miRNA-29a/b/c expression patterns but the amount of miRNA-29a/b/c, IL-32 isoforms and MxA were highly variable in these two cellular subsets. CONCLUSIONS: The miRNA-29 family could influence the clinical progression of HIV-1 infection, the HIV-1 proviral load and the innate immune response against HIV-1

Autonomous pick-and-place using the dVRK.

PURPOSE: Robotic-assisted partial nephrectomy (RAPN) is a tissue-preserving approach to treating renal cancer, where ultrasound (US) imaging is used for intra-operative identification of tumour margins and localisation of blood vessels. With the da Vinci Surgical System (Sunnyvale, CA), the US probe is inserted through an auxiliary access port, grasped by the robotic tool and moved over the surface of the kidney. Images from US probe are displayed separately to the surgical site video within the surgical console leaving the surgeon to interpret and co-registers information which is challenging and complicates the procedural workflow. METHODS: We introduce a novel software architecture to support a hardware soft robotic rail designed to automate intra-operative US acquisition. As a preliminary step towards complete task automation, we automatically grasp the rail and position it on the tissue surface so that the surgeon is then able to manipulate manually the US probe along it. RESULTS: A preliminary clinical study, involving five surgeons, was carried out to evaluate the potential performance of the system. Results indicate that the proposed semi-autonomous approach reduced the time needed to complete a US scan compared to manual tele-operation. CONCLUSION: Procedural automation can be an important workflow enhancement functionality in future robotic surgery systems. We have shown a preliminary study on semi-autonomous US imaging, and this could support more efficient data acquisition

Superinfections in patients treated with teicoplanin as anti SARSCoV2 AGENT

We read with interest the paper by Giacobbe et al. estimating a cumulative risk of developing at least one bloodstream infection (BSI) episode (largely due to Gram-positive pathogens) of almost 50% after 30 days at risk in (2) Similarly, Somers et al. reported an increased risk to develop bacterial superinfections, principally represented by Staphylococcus aureus ventilatory associated pneumonia (VAP), in critically ill patients infected with SARS-CoV-2 and treated with Tocilizumab. (1) We previously described a cohort of intubated patients affected by severe COVID-19pneumonia treated with the best available therapy (BAT), including Tocilizumab and associated with Teicoplanin. (3) This glycopeptide antibiotic was used with a double purpose: as antiviral agent for COVID-19 and as of possible S.aureus superinfection

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]

Antiviral activity of fecal water samples from HIV-1 infected subjects treated with a specific probiotic formulation

Objectives: The aim of the study was to investigate if the supplementation with multistrain probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate the anti-HIV activity of probiotic by studying fecal water (FW) samples. Methods: Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on long-term suppressive combined antiretroviral therapy (cART) received a specific multi-strain probiotic supplementation (Vivomixx ®), for six months (T6). Levels of T cell subsets were evaluated by flow cytometry. Anti- HIV activity of FW samples was evaluated in vitro. Results: CD4+ T cells levels increased in all HIV-1 infected patients whereas activation markers (CD38 and HLA-DR) were decreased both on CD4+ and CD8+ T cells. FW samples presented an increased inhibitory activity against HIV-1 compared to T0 (FW-Pt1: T0 =40%, T6 = 65% of reduction; FW Pt2: T0 = 26%, T6 = 46% of reduction; FW Pt3: T0 = 47%, T6 = 94% of reduction). Discussion: Our data suggest that the administration of the specific probiotic formulation improves the antiviral status of people living with HIV-1 under cART, also modulating T cell response. Conclusion: Anti-HIV activity of FW may have several public health and social implications for sexually transmitted diseases that need to be further explored

Preliminary attempt to predict risk of invasive pulmonary aspergillosis in patients with influenza. Decision trees may help?

Invasive pulmonary aspergillosis (IPA) is typically considered a disease of immunocompromised patients, but, recently, many cases have been reported in patients without typical risk factors. The aim of our study is to develop a risk predictive model for IPA through machine learning techniques (decision trees) in patients with influenza. We conducted a retrospective observational study analyzing data regarding patients diagnosed with influenza hospitalized at the University Hospital “Umberto I” of Rome during the 2018-2019 season. We collected five IPA cases out of 77 influenza patients. Although the small sample size is a limit, the most vulnerable patients among the influenza-infected population seem to be those with evidence of lymphocytopenia and those that received corticosteroid therapy

Analysis of type I IFN response and T cell activation in severe COVID-19/HIV-1 coinfection. A case report

RATIONALE: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women. PATIENT CONCERNS: A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study. DIAGNOSES: SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities. INTERVENTIONS: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/β mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative. OUTCOMES: The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/β and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/β: median -0.2545 (range: -0.5/0.1); T cells: median -0.11 (range: -0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/β: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]. LESSONS: These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/β-mRNAs and T cell activation compared to healthy individuals