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Background. The ultimate goal of organ transplantation is the reestablishment of organ function and the restoration of a solid immunity to prevent the assault of potentially deadly pathogens. T cell immunity is crucial in controlling cytomegalovirus (CMV) infection. It is still unknown how preexisting antiviral T cell levels, prophylaxis, or preemptive antiviral strategies and pharmacological conditioning affect immune reconstitution. Methods. Seventy preemptively treated CMV-seropositive recipients, 13 prophylaxis-treated CMV-seronegative recipients of seropositive donor transplants, 2 seropositive recipients of seronegative donor kidneys, and 27 pretransplant subjects were enrolled in a cross-sectional study and analyzed for CMV viremia (DNAemia) and CMV-specific T cell response (interferon-gamma enzyme-linked immunospot assay) before transplantation and at 30, 60, 90, 180, and 360 days after transplantation. Results. CMV-seropositive transplant recipients displayed a progressive but heterogeneous pattern of immune reconstitution starting from day 60 after transplantation. CMV-seronegative recipients did not mount a detectable T cell response throughout the prophylaxis regimen. A single episode of CMV viremia (CMV copy number, 7000-170,000 copies/mL) was sufficient to prime a protective T cell immune response in CMV-seronegative recipients. Antithymocyte globulin treatment did not significantly affect CMV-specific T cell response. Conclusions. Baseline immunity, antiviral therapy but not antithymocyte globulin treatments profoundly influence T cell reconstitution in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Aim: Aim of the present study was to investigate the relationship between CMV and EBV infection and the occurrence of antibody mediated rejection (AMR) in a cohort of adult heart transplant recipients (HTXs).Materials and Methods: 47 adult HTX patients were enrolled in a case-control study from June 2010 to June 2012, 24 of them with humoral rejection and 23 without.Endomyocardial biopsies (EMBs) were routinely performed and pathological diagnosis of AMR assessed according to ISHLT 2011. Donor specific antibodies titles were evaluated at the same time of EMBs biopsy. Routine surveillance for viral reactivation or infection comprised weekly determination of whole blood CMV DNAemia during the first 100 days post-transplant. CMV and EBV DNAemia was evaluated using real-time PCR. We divided the cohort study in two groups according to time since HTx as early (1-90 days) and late (91-360 days).Results: In the AMR group the EBV infection was present in 13 cases (13/24, 54%) and CMV in 10 cases (10/24, 42%). In the control group the cases of pts with EBV were 2/23 (9%), while CMV were 4/23 (17%).In the early period EBV infection was present in 12/24 cases (50%, p=0.000) and CMV infection was present in 10/23 cases (p=0.042). In the late period EBV was present in 6/24 cases (25%, p=0.002) and CMV in 1/23 (4%, p=0.000).Conclusions: EBV and CMV infections during follow-up post heart transplantation occurred more frequently in patients with AMR suggesting that virus could act as a trigger in humoral rejection. [ABSTRACT FROM PUBLISHER]

Background: Antibody-mediated rejection (AMR) is a serious complication affecting the survival of patients receiving transplantation. Human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common viral infections that occur after transplantation, frequently emerging as viral reactivation in donor grafts or transplant recipients. The present study aimed to investigate the association between CMV and EBV infections and early-onset AMR., Materials and Methods: This study was conducted at the Heart Transplantation Center of Padova General Hospital and included a cohort of 47 heart transplant recipients (HTxs), including 24 HTxs diagnosed with AMR and 23 control HTxs with no episodes of AMR. Only early cases of CMV and/or EBV infections (1-90 days after transplantation) were considered. Fisher's exact test and logistic regression analysis were used to statistically analyze the correlation and association between AMR and CMV or EBV infection., Results: We observed a positive statistical association between CMV and EBV infections (two-sided Fisher's exact test, p = 0.0136) and between EBV infection and AMR (two-sided Fisher's exact test, p = 0.0034). Logistic regression analysis revealed a direct statistical association between CMV and EBV infections and AMR risk (p = 0.037 and 0.006 and odds ratio = 1.72 and 2.19, respectively). AMR occurrence was associated with increased viral loads of both CMV and EBV early after transplantation., Discussion: These findings suggest the role of CMV and EBV infections as relevant risk factors for AMR in HTxs for the first time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saldan, Mengoli, Sgarabotto, Fedrigo, Angelini, Feltrin, Gambino, Gerosa, Barzon and Abate.)

This is a retrospective study of our experience with Gentamicin intravesical instillation as therapy and prophylaxis in patients with lower urinary tract infections (UTIs) undergoing clean intermittent catheterization because of a neurogenic bladder. It is an alternative therapy when all other systemic treatments have failed as it is still an off-label prescription.

This study is a retrospective epidemiological assessment of bacterial species isolated from a cohort of out-patients with diabetic foot infections referred to our "Diabetic Foot Unit" over one year, with particular attention to index pathogens, as identified by the EARS Network. Staphylococcus aureus and Pseudomonas aeruginosa accounted for 33.5% and 11.9% of cases, respectively. MRSA was isolated in 27.1% of patients, with 14.06% showing additional resistance to three antimicrobial classes. Pseudomonas aeruginosa presented extensive resistance to fluoroquinolones (57.3%), which was associated with resistance to piperacillin in 17.6% or to carbapenems in 23.5% of cases. Other pathogens, such as methicillin resistant Staphylococcus epidermidis , Escherichia coli and Morganella morganii ESBL and Enterococcus faecium VRE, were also found.

Plasmodium knowlesi is a simian parasite responsible for most human cases of malaria in Malaysian Borneo. A timely recognition of infection is crucial because of the risk of severe disease due to the rapid increase in parasitemia. We report a case of P. knowlesi infection in a traveller who developed fever and thrombocytopenia after returning from the Philippines in 2016. Rapid antigen test was negative, microscopy examination showed parasites similar to Plasmodium malariae, with a parasite count of 10,000 parasites per μL blood, while molecular testing identified P. knowlesi infection. Treatment with atovaquone-proguanil led to resolution of fever and restoration of platelet count in two days. P. knowlesi infection should be suspected in febrile travellers returning from South East Asia. Due to the low sensitivity of rapid antigen tests and the low specificity of microscopy, confirmation by molecular tests is recommended.

We describe the dynamics of Zika virus (ZIKV) infection in a man in his early 40s who developed fever and rash after returning from Haiti to Italy, in January 2016. Follow-up laboratory testing demonstrated detectable ZIKV RNA in plasma up to day 9 after symptom onset and in urine and saliva up to days 15 and 47, respectively. Notably, persistent shedding of ZIKV RNA was demonstrated in semen, still detectable at 181 days after onset., Competing Interests: Conflicts of Interest: None declared., (This article is copyright of The Authors, 2016.)

Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMV-specific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R+) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D+/R-). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P<0.05). During the antiviral prophylaxis, all 20 D+/R- KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.

Human cytomegalovirus (CMV) infection represents a major threat for heart transplant recipients (HTXs). CMV-specific T cells effectively control virus infection, and thus, assessment of antiviral immune recovery may have clinical utility in identifying HTXs at risk of infection. In this study, 10 CMV-seropositive (R(+)) pretransplant patients and 48 preemptively treated R(+) HTXs were examined before and after 100 days posttransplant. Preemptive treatment is supposed to favor the immune recovery. CMV DNAemia and gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay were employed to assess the viremia and immune reconstitution. HTXs could be categorized into three groups characterized by high (>100), medium (50 to 100), and low (<50) spot levels. Early-identified high responders efficiently controlled the infection and also maintained high immunity levels after 100 days after transplant. No episodes of grade ≥2R rejection occurred in the high responders. Midresponders were identified as a group with heterogeneous trends of immune reconstitution. Low responders were 41% and 21% of HTXs before and after 100 days posttransplant, respectively. Low responders were associated with a higher incidence of infection. The effect of viremia on immune recovery was investigated: a statistically significant inverse correlation between magnitude of viremia and immune recovery emerged; in particular, each 10-fold increase in viremia (>4 log(10) DNAemia/ml) was associated with a 36% decrease of the ELISPOT assay spot levels. All episodes of high viremia (>4 log(10) DNAemia/ml) occurred from 1 to 60 days after transplant. Thus, the concomitant evaluation of viremia and CMV immune reconstitution has clinical utility in identifying HTXs at risk of infection and may represent a helpful guide in making therapeutic choices.

Few studies have been performed on the prevalence of Torque Teno Virus (TTV) infection in liver transplant (LT) recipients. The aim of this study was to assess the prevalence, viremia and genogroup pattern of TTV among LT patients and to ascertain whether TTV causes liver damage in liver transplanted patients with biochemical and histological changes of unknown origin. Twenty-five patients were evaluated before and after LT; 80 healthy subjects were considered as controls. Serum samples were serially obtained from all the patients before LT and thereafter at 3, 6 and 12 months post-transplant. Serum TTV-DNA and genogroups were assessed by PCR. Patients underwent protocol serial liver biopsies at 6 and 12 months after LT. Results were compared using the Chi-squared tests, McNemar's and Student's t-tests. TTV-DNA was found in 25/25 patients before LT and in 60/80 blood donors (P < 0.01). The TTV-DNA load increased significantly after LT (P < 0.001). TTV-DNA was significantly higher in patients on calcineurin inhibitors (CNI) and azathioprine or mycophenolate mofetil than in patients on CNI alone (P = 0.04) at 3 months after LT. Genogroup analysis showed a significant increase in genogroup 5 positivity after LT. No differences were seen in the viremia of patients compared according to their viral versus other etiologies of their liver disease before transplantation. Viremia and TTV genotype patterns did not correlate with the presence of hypertransaminasemia or histological liver damage of unknown etiology. The prevalence of TTV-DNA was significantly higher in patients with liver cirrhosis than in controls and the viral load was significantly higher after LT than beforehand. On the basis of our data, TTV does not seem to cause liver damage following LT, although larger studies with a long-term follow up are needed to confirm these findings.

Different animal studies show that several proinflammatory cytokines are essential for natural resistance to specific infections, particularly versus intracellular organisms. However, uncontrolled overproduction of some proinflammatory cytokines, in diseases such as rheumatoid arthritis, can be just as dangerous to the host as the absence of the same cytokines. Reduction in the production and/or activities of proinflammatory cytokines in rheumatoid arthritis remains a therapeutic objective for many patients. The tumour necrosis factor-alpha (TNF-alpha) blockers infliximab, etanercept and adalimumab and the recombinant interleukin 1 (IL-1) receptor antagonist anakinra are effective in patients with active rheumatoid arthritis. However, there is a growing body of clinical evidence that neutralization of TNF-alpha is associated with an increased risk of opportunistic infections, including mycobacterial diseases. Blockade of IL-1 activity with the IL-1 receptor antagonist (IL-1Ra) appears, at present, to be relatively safe. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. At this time, treating physicians must weigh carefully the benefits of biologics against their safety, particularly in patients at risk of infection.

Background and Objective: Approximately 15% of patients with cancer will experience a thrombotic episode at some time. Some patients are at particularly high risk depending on the histology of the malignant disease. The aim of the study was to determine the actual prevalence of thrombotic episodes in oncohematologic patients., Design and Methods: We conducted a retrospective cohort analysis on a total of 515 patients that were admitted to the out-patients clinic (Institute of Medical Semeiotics) from January 1, 1986 to January 31, 1996. Two main groups were selected for this study: 133 patients suffering from a myeloproliferative disorder and 382 patients affected by a lymphoproliferative disorder. Follow-up lasted a median of 33 months in both groups (range 3-144 months). The difference between the observed events for each group was estimated by the odds ratio and chi square. Age and sex distribution were estimated by the Mann-Whitney test. Distribution of overall survival was estimated by the Kaplan-Meier method and compared between groups (DVT patients and non DVT patients) by the log-rank test., Results: Twenty-three patients experienced a venous thrombotic disorder. The prevalence of deep vein thrombosis (DVT) in myeloproliferative and lymphoproliferative disorders was 8.27% (n = 11) and 3.14% (n = 12) respectively (odds ratio = 0.36; 95% CI = 0.14-0.90; chi-square = 4.94 p = 0.028). DVT was apparently idiopathic in 17 cases. In 4 patients another cancer was present; in the remaining 2 patients the thrombotic episode was associated with other predisposing factors. Although 7 of the 23 patients with DVT died, we cannot find any difference in the overall survival compared to oncohematologic patients who did not experience DVT., Interpretation and Conclusions: The prevalence of symptomatic DVT in the oncohematological patients is lower than reported for solid tumor. Patients affected by myeloproliferative disease have a higher risk of developing thrombosis. DVT if well-treated does not influence the survival of oncohematological patients.