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SETTING: Multidrug-resistant TB (MDR-TB) clinical trial in Lima, Peru and Cape Town, South Africa.OBJECTIVE: To identify baseline factors associated with screening failure and study withdrawal in an MDR-TB clinical trial.DESIGN: We screened patients for a randomized, blinded, Phase II trial which assessed culture conversion over the first 6 months of treatment with varying doses of levofloxacin plus an optimized background regimen (ClinicalTrials.gov: NCT01918397). We identified factors for screening failure and study withdrawal using Poisson regression to calculate prevalence ratios and Cox proportional hazard regression to calculate hazard ratios. We adjusted for factors with P < 0.2.RESULTS: Of the 255 patients screened, 144 (56.5%) failed screening. The most common reason for screening failure was an unsuitable resistance profile on sputum-based molecular susceptibility testing (n = 105, 72.9%). No significant baseline predictors of screening failure were identified in the multivariable model. Of the 111 who were enrolled, 33 (30%) failed to complete treatment, mostly for non-adherence and consent withdrawal. No baseline factors predicted study withdrawal in the multivariable model.CONCLUSION: No baseline factors were independently associated with either screening failure or study withdrawal in this secondary analysis of a MDR-TB clinical trial.

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Background: Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19. Methods: We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086. Findings: Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC (n = 42), Low-volume (n = 43) or High-volume (n = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion. Interpretation: In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits. Funding: Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.

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OBJECTIVES: Evaluate the impact of ABO histo-blood group type on COVID-19 severity. BACKGROUND: ABO histo-blood type has been associated with different outcomes in infectious diseases. It has also shown a higher proportion of type A patients with SARS-CoV-2. In this observational study, extracted from an ongoing clinical trial on the efficacy of convalescent plasma transfused in COVID-19 patients, we describe the impact of ABO blood type on the risk of developing severe COVID-19. MATERIALS AND METHODS: Seventy-two consecutive patients (37 type A, 23 type O, 11 type B, 1 type AB) with severe (respiratory failure) COVID-19 were included. Control group was composed of 160 individuals randomly selected from the same populational basis. RESULTS: Blood group A was overrepresented (51.39%) in the patient group in relation to the control group (30%), whereas blood group O was less represented (31.94%) in patient than in control group (48%). Odds ratio (A vs. O) was 2.581 (1.381-4.817), CI 95%; p = 0.004. Also, blood group A patients appeared to have more severe disease, given by the scores of the Sequential Organ Failure Assessment and Simplified Acute Physiologic Score 3 (p = 0.036 and p = 0.058, respectively). CONCLUSION: Histo-blood type A is associated with a higher risk of developing severe COVID-19 in relation to blood type O.

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Brucella lumazine synthase (BLS) is a homodecameric protein that activates dendritic cells via toll like receptor 4, inducing the secretion of pro-inflammatory cytokines and chemokines. We have previously shown that BLS has a therapeutic effect in B16 melanoma-bearing mice only when administered at early stages of tumor growth. In this work, we study the mechanisms underlying the therapeutic effect of BLS, by analyzing the tumor microenvironment. Administration of BLS at early stages of tumor growth induces high levels of serum IFN-γ, as well as an increment of hematopoietic immune cells within the tumor. Moreover, BLS-treatment increases the ratio of effector to regulatory cells. However, all treated mice eventually succumb to the tumors. Therefore, we combined BLS administration with anti-PD-1 treatment. Combined treatment increases the outcome of both monotherapies. In conclusion, we show that the absence of the therapeutic effect at late stages of tumor growth correlates with low levels of serum IFN-γ and lower infiltration of immune cells in the tumor, both of which are essential to delay tumor growth. Furthermore, the combined treatment of BLS and PD-1 blockade shows that BLS could be exploited as an essential immunomodulator in combination therapy with an immune checkpoint blockade to treat skin cancer.

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CASE REPORT: A 26-year-old woman with sickle cell disease (SCD) on chronic transfusion therapy complained of severe arthralgia, myalgia, abdominal pain, headache, and fever 24 hours after transfusion of a red blood cells (RBCs). Dengue virus (DENV) infection was suspected and the patient was hospitalized for clinical support and RBC transfusion, to lower the hemoglobin S to less than 30%. The patient's clinical condition improved approximately 8 days after the onset of symptoms. RESULTS: DENV type 2 (DENV-2) TaqMan real-time polymerase chain reaction was negative in the patient's pretransfusion sample while the posttransfusion sample was positive (Ct, 27.8), suggesting a high viral load and an acute infection. To investigate DENV transfusion transmission (TT-DENV) the stored donor serum was tested and was also positive (Ct, 25.8). Molecular typing confirmed the presence of DENV-2. The phylogenetic analysis of the DENV-2 strains obtained from both donor and patient samples were classified as the Southeast Asia-American genotype (Genotype III) and demonstrated 100% genomic identity, indicating TT-DENV. CONCLUSION: This is the first description of TT-DENV in a SCD patient. A presumed high viral load in the transfused RBC unit probably determined the early clinical manifestation. In endemic regions dengue fever should be considered as differential diagnosis in SCD patients with fever and acute pain crisis, mainly during DENV outbreaks.

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RESUMEN La orquídea Cattleya trianae Linden & Rchb.f. es reconocida como flor nacional de Colombia y se encuentra en peligro crítico, al presentar una reducción estimada mayor al 80% en los últimos 100 años, debido a la disminución en la calidad del hábitat y niveles altos de explotación o recolección. La familia Orchidaceae es una de las que mayor número de especies posee en el reino Plantae, con aproximadamente 900 géneros, de los cuales, el 38% es endémico de Colombia, concentrado en la región Andina, con 87,2%. Esta investigación buscó profundizar en el tema de la propagación como mecanismo de conservación, para lo cual, se determinó el efecto de la 6-Bencilaminopurina (6-BAP), sobre el desarrollo in vitro, en Fusagasugá (Cundinamarca), en un diseño de bloques completamente al azar, con 3 repeticiones. Cuerpos protocórmicos provenientes de semillas recolectadas en Pacho (Cundinamarca) fueron sembrados en medio básico Murashige & Skoog, enriquecido con 4 concentraciones de 6-BAP. Los resultados mostraron respuestas diferenciales a la adición de la citoquinina, ya que, con la concentración más alta, se obtuvo el mayor porcentaje de callos, con la de 0,05mg.L-1, el mayor porcentaje de brotes y sin la aplicación del regulador de crecimiento, el mayor porcentaje de raíz.

ABSTRACT The orchid Cattleya trianae Linden & Rchb.f. is recognized as the national flower of Colombia, the species is in a critical danger, presenting an estimated reduction of more than 80% in the last 100 years due to the decrease in habitat quality and high levels of exploitation or harvesting. The Orchidaceae family is one of the largest number of species in the Plant Kingdom, with approximately 900 genera, of which 38% are endemic in Colombia, concentrated in the Andean region with 87.2%. This research sought to deepen in the topic of the propagation as mechanism of protection for their conservation, for which the effect of cytokinin 6-benzylaminopurine (6-BAP) on development was determined in vitro in Fusagasugá (Cundinamarca), in a completely randomized block design with 3 replicates. The protocorm-like bodies from seeds collected in Pacho (Cundinamarca) were sown in a basic medium Murashige and Skoog enriched with 4 concentrations of 6-BAP. The results showed differential responses to the addition of cytokinin, as the highest concentration was obtained the highest percentage of callus, with the 0.05mg. L-1, the highest percentage of shoots and without the application of the growth regulator, the highest root percentage.

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