Objective: To determine the role of urine cytology for ‘decoy cells’ as a screening tool for polyomavirus type BK (BKV) infection in renal transplant recipients. Study Design: This was a prospective cohort study of patients undergoing renal transplantation between 2006 and 2010. Results: A total of 442 patients underwent urine cytology for decoy cells, 27.8% underwent 1 examination only and 72.2% more than one. Of the 1,713 examinations reviewed, 426 (24.9%) were positive and 785 (45.8%) were negative for ‘decoy’ cells, 380 (22.2%) showed degenerated tubular cells and 122 (7.1%) were unsatisfactory for analysis. Urine cytology was found to have a specificity of 68.5%, a sensitivity of 84.6%, a positive predictive value of 21.2%, a negative predictive value of 97.8% and an overall accuracy of 69.9%. The incidence of polyomavirus nephropathy among the patients investigated was 11.8%. Of the 442 patients, 32 (7.2%) had graft loss, which was attributed to BKV nephropathy in 2 (6.2% of the 32). Conclusions: Urine cytology is an effective screening method for monitoring renal transplant patients, with high sensitivity and a high negative predictive value, and can therefore be used routinely in the follow-up of renal transplant patients.

The mTOR (mammalian or mechanistic Target Of Rapamycin), a complex metabolic pathway that involves multiple steps and regulators, is a major human metabolic pathway responsible for cell growth control in response to multiple factors and that is dysregulated in various types of cancer. The classical inhibition of the mTOR pathway is performed by rapamycin and its analogs (rapalogs). Considering that rapamycin binds to an allosteric site and performs a crucial role in the inhibition of the mTOR complex without causing the deleterious side effects common to ATP-competitive inhibitors, we employ ligand-based drug design strategies, such as virtual screening methodology, computational determination of ADME/Tox properties of selected molecules, and molecular dynamics in order to select molecules with the potential to become non-ATP-competitive inhibitors of the mTOR enzymatic complex. Our findings suggest five novel potential mTOR inhibitors, with similar or better properties than the classic inhibitor complex, rapamycin.

Background Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. Methods Prospective randomized multicenter open-label trial of one or two-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) Single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. Results A total of 118 subjects were randomizedMedian CD4+ counts and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for Single-dose L-AmB, 69% Two-dose L-AmB, and 74% Control arm (p=0.69). Overall survival on D14 was 89.0% (34/38) for Single-dose L-AmB, 78.0% (29/37) for Two-dose L-AmB, and 92.1% (35/38) for Control arm (p=0.82). Conclusions One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

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Introduction: Acute kidney injury (AKI) occurs in about 22% of the patients undergoing cardiac surgery and 2.3% requires renal replacement therapy (RRT). The current diagnostic criteria for AKI by increased serum creatinine levels have limitations and new biomarkers are being tested. Urine sediment may be considered a biomarker and it can help to differentiate pre-renal (functional) from renal (intrinsic) AKI. Aims: To investigate the microscopic urinalysis in the AKI diagnosis in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: One hundred and fourteen patients, mean age 62.3 years, 67.5 % male, with creatinine 0.91 mg/dL (SD 0.22) had a urine sample examined in the first 24 h after the surgery. We looked for renal tubular epithelial cells (RTEC) and granular casts (GC) and associated the results with AKI development as defined by KDIGO criteria. Results: Twenty three patients (20.17 %) developed AKI according to the serum creatinine criterion and 76 (66.67 %) by the urine output criterion. Four patients required RRT. Mortality was 3.51 %. The use of urine creatinine criterion to predict AKI showed a sensitivity of 34.78 % and specificity of 86.81 %, positive likelihood ratio of 2.64 and negative likelihood ratio of 0.75, AUC-ROC of 0.584 (95%CI: 0.445-0.723). For the urine output criterion sensitivity was 23.68 % and specificity 92.11 %, AUC-ROC was 0.573 (95%CI: 0.465-0.680). Conclusion: RTEC and GC in urine sample detected by microscopy is a highly specific biomarker for early AKI diagnosis after cardiac surgery.

Background The molecular dynamics is an approach to obtain kinetic and thermodynamic characteristics of biomolecular structures. The molecular dynamics simulation softwares are very useful, however, most of them are used in command line form and continue with the same common implementation difficulties that plague researchers who are not computer specialists. Results Here, we have developed the VisualDynamics—a WEB tool developed to automate biological simulations performed in Gromacs using a graphical interface to make molecular dynamics simulation user-friendly task. In this new application the researcher can submit a simulation of the protein in the free form or complexed with a ligand. Can also download the graphics analysis and log files at the end of the simulation. Conclusions VisualDynamics is a tool that will accelerate implementations and learning in the area of molecular dynamics simulation. Freely available at https://visualdynamics.fiocruz.br/login, is supported by all major web browsers. VisualDynamics was developed with Flask, which is a Python-based free and open-source framework for web development. The code is freely available for download at GitHub https://github.com/LABIOQUIM/visualdynamics.

Background Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. Methods This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). Results Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients’ mean age was 30 years (24–40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01–0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00–0.28], p = 0.002 in the eculizumab Therapeutic Group. Conclusion The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries.

Background: Bioimpedance analysis (BIA) has been demonstrated to add accuracy to nutritional and volume status assessments in dialysis (HD) patients. Aim: to describe a sample of dialysis patients from a single center on their demographics and BIA of volume distribution and nutritional status, and mortality during 12-month follow-up. Methods: prospective observational cohort study to evaluate vintage HD patients with single-frequency BIA. Results: we evaluated 82 patients, 29% over 65 years old. Elderly patients had higher ECW/TBW (0.51 vs. 0.44, p < 0.0001), and narrower phase angle (PhA) (4.9 vs. 6.4º, p < 0.0001). Fifteen patients (18.2%) died during follow-up, eight (53%) were elderly. Death was associated with age (62.6 vs. 50.2 years, p = 0.012), post-HD PhA (4.8 vs. 6.2º, p = 0.0001), and post-HD ECW/TBW (0.50 vs. 0.45, p = 0.015). The ROC curve analysis to predict mortality found ECW/TBW ≥ 0.47 and PhA ≤ 5.5º to have the best sensitivity and specificity. One-year patient survival was lower with post-HD ECW/TBW ≥ 0.47 (69.5% vs. 90.6%, p = 0.019), age ≥ 65 years (64.2%, vs. 86.2%, p = 0.029), and PhA ≤ 5.5º (68.2 vs. 91.0%, p = 0.002). Cox regression analysis demonstrated that PhA [HR 5.04 (95%CI 1.60–15.86), p = 0.006] remained associated with death after adjusting for age and ECW/TBW. Conclusion: BIA is useful in assessing volume distribution and nutrition in HD patients, and combined with clinical judgement, may help determine dry weight, especially in elderly patients. Narrower PhA and higher ECW/TBW after HD were associated with poorer one-year survival.