COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.     

Quantifying convergence on health-related indicators of the 2030 agenda for sustainable development

The extended scope and complexity of the United Nations 2030 agenda entail important challenges for the operationalization of the health-related sustainable development goal (SDG) indicators. Divergences in concepts, agendas and implementation strategies among institutions have fostered the parallel development of alternative and concurrent indicators. We aim to determine the convergences and divergences between five key institutions: the Global Burden of Disease Study (GBD), the Pan American Health Organization, the Sustainable Development Solutions Network, the World Bank and the World Health Organization (WHO). Of the 104 health-related indicators listed by these five institutions, 60 are consistent with official Inter-agency and Expert Group SDG indicators. Our analysis considers the indicators included, and the themes these indicators cover, in each institution list and each institution online platform. We quantified convergence in indicators between the institutions themselves, but also between the institutions and the official Inter-agency and Expert Group. Our results indicate important divergences; only 22 of the 60 indicators are included in the lists of all five institutions. The level of adoption of the official metrics varies from 40.5% (15/(47−10)) for the GBD to 86.2% (25/(29−0)) for the World Bank. WHO, the official curator of the Inter-agency and Expert Group SDG indicators, is only convergent with the official metrics by 72.1% (31/(45−2)). Our analysis, and the resulting awareness of the differences, potentialities and limitations of indicators and platforms, provides important contributions to enable the achievement of the health-related SDGs and deliver the promise of the 2030 agenda.     

IMXQB-80: A Quillaja brasiliensis saponin-based nanoadjuvant enhances Zika virus specific immune responses in mice

Vaccine adjuvants are compounds that enhance/prolong the immune response to a co-administered antigen. Saponins have been widely used as adjuvants for many years in several vaccines – especially for intracellular pathogens – including the recent and somewhat revolutionary malaria and shingles vaccines. In view of the immunoadjuvant potential of Q. brasiliensis saponins, the present study aimed to characterize the QB-80 saponin-rich fraction and a nanoadjuvant prepared with QB-80 and lipids (IMXQB-80). In addition, the performance of such adjuvants was examined in experimental inactivated vaccines against Zika virus (ZIKV). Analysis of QB-80 by DI-ESI-ToF by negative ion electrospray revealed over 29 saponins that could be assigned to known structures existing in their congener Q. saponaria, including the well-studied QS-21 and QS-7. The QB-80 saponins were a micrOTOF able to self-assembly with lipids in ISCOM-like nanoparticles with diameters of approximately 43 nm, here named IMXQB-80. Toxicity assays revealed that QB-80 saponins did present some haemolytical and cytotoxic potentials; however, these were abrogated in IMXQB-80 nanoparticles. Regarding the adjuvant activity, QB-80 and IMXQB-80 significantly enhanced serum levels of anti-Zika virus IgG and subtypes (IgG1, IgG2b, IgG2c) as well as neutralized antibodies when compared to an unadjuvanted vaccine. Furthermore, the nanoadjuvant IMXQB-80 was as effective as QB-80 in stimulating immune responses, yet requiring fourfold less saponins to induce the equivalent stimuli, and with less toxicity. These findings reveal that the saponin fraction QB-80, and particularly the IMXQB-80 nanoadjuvant, are safe and capable of potentializing immune responses when used as adjuvants in experimental ZIKV vaccines.     

Experimental cutaneous leishmaniasis. III. Histopathological aspects of the developmental behavior of the cutaneous lesion induced in Cebus apella (Primates: Cebidae) by Leishmania (Viannia) lainsoni, L. (V.) braziliensis and L. (Leishmania) amazonensis

We have studied the histopathological aspects related to the evolution of cutaneous lesions experimentally produced in the monkey Cebus apella (Primates: Cebidae) by Leishmania (V.) lainsoni, L. (V.) braziliensis and L. (L.) amazonensis. Microscopical examination of a series of biopsies obtained from these animals showed the kinetics of the cutaneous lesions regarding three species of Leishmania inoculated, as follows: 1) an initial non-specific chronic inflammatory infiltrate; 2) macrophagic nodules; 3) necrosis of parasitized phagocytic cells; 4) epitheliode granuloma; 5) absorption of the necrotic area (sometimes forming "foreign-body granuloma"); 6) a non-specific residual inflammatory infiltration; and 7) cicatrization. These pathological processes are, of course, responsible for both development and resolution of the leishmaniotic lesion. We also discuss some immunopathological mechanisms probably related with the sequential events, and that could be also responsible for the different clinical aspects found in man.     

Management of occult intrasacral meningocele associated with lumbar disc prolapse

Occult intrasacral meningocele is an uncommon condition that may produce chronic low back pain, sciatica, and bladder dysfunction. We describe a patient suffering from low back pain and radicular symptoms, in whom multimodality radiological examinations showed an intrasacral meningocele and a lumbar disc prolapse. The protuded disc was considered to be the cause of the clinical symptoms in this patient rather than the meningocele. Surgical removal of the protuded disc was performed without interference with the meningocele. Postoperatively there was recovery of the preoperative deficits. Clinical and radiographic findings in occult intrasacral meningocele are discussed and criteria for differential diagnosis with disc prolapse are stressed.     

Quinolone prophylaxis in neutropenic patients - efficacy versus resistance

To assess the efficacy of quinolones in the prophylaxis of infections in neutropenic patients with acute non-lymphocytic leukemia, and to evaluate the emergence of quinolone resistance in two University Hospitals in Brazil, we retrospectively compared 101 consecutive episodes of neutropenia managed with quinolone prophylaxis between 1989 and November 1993, and 26 previous episodes without prophylaxis, and reviewed the results of in vitro sensitivity of Gram-negative strains to quinolones in the same period. Prophylaxis with quinolones resulted in less episodes of bacteremias (21% vs. 69%, p=10(-7)), including Gram-negative bacteremias (6% vs. 38%, p=10(-5)), with no statistically significant difference in the death rate (18% vs. 31%, p=0.14, 95% confidence interval -6-32). The resistance of Gramnegative strains to quinolones rose from 7% to 18% between 1990 and 1993 (p=10(-5)). The resistance against ceftazidime and amikacin, the agents used in the empirical antibiotic therapy, increased in the same proportion as the quinolones. Given the limited benefit of quinolones as prophylaxis and the increasing number of quinolone-resistant Gram-negative strains observed in our hospitals, the use of quinolones as prophylaxis must be seriously questioned. A stricter control of the use of quinolones in these hospitals might decrease resistance.