Background: Pneumocystis jirovecii pneumonia (PJP) can be a life-threatening opportunistic infection in immunocompromised hosts. The diagnosis can be challenging, often requiring semi-invasive respiratory sampling. The serum 1,3-b-D-glucan (BDG) assay has been proposed as a minimally invasive test for the presumptive diagnosis of PJP. Method: We carried out a systematic review and meta-analysis using articles in the English language published between January 1960 and September 2019. We estimated the pooled sensitivity and specificity of BDG testing using a bivariate random effects approach and compared test performance in human immunodeficiency virus (HIV) and non-HIV subgroups with meta-regression. Data from the pooled sensitivity and specificity were transformed to generate pre-and post-test probability curves. Results: Twenty-three studies were included. The pooled sensitivity and specificity of serum BDG testing for PJP were 91% (95%CI 87e94%) and 79% (95%CI 72e84%) respectively. The sensitivity in patients with HIV was better than in patients without (94%, 95%CI 91e96%) versus 86% (95%CI 78e91%) (p 0.02), with comparable specificity (83%, 95%CI 69e92% versus 83%, 95%CI 72e90%) (p 0.10). A negative BDG was only associated with a low post-test probability of PJP (5%) when the pre-test probability was low to intermediate (20% in non-HIV and 50% in HIV). Conclusions: Among patients with a higher likelihood of PJP, the pooled sensitivity of BDG is insufficient to exclude infection. Similarly, for most cases, the pooled specificity is inadequate to diagnose PJP. Understanding the performance of BDG in the population being investigated is therefore essential to optimal clinical decision-making.
Zika virus (ZIKV) is an emerging pathogen from the Flaviviridae family. It represents a significant threat to global health due to its neurological and fetal pathogenesis (including microcephaly and congenital malformations), and its rapid dissemination across Latin America in recent years. The virus has spread from Africa to Asia, the Pacific islands and the Americas with limited knowledge about the pathogenesis associated with infection in recent years. Herein, we compared the ability of the Canadian-imported Thai strain PLCal_ZV and the Brazilian isolate HS-2015-BA-01 from Bahia to produce infectious ZIKV particles and cytopathic effects in a cell proliferation assay. We also compared the intracellular viral RNA accumulation of the two strains by quantitative RT-PCR (reverse transcription polymerase chain reaction) analyses. Our observations show that HS-2015-BA-01 is more cytopathic than PLCal_ZV in proliferation assays in Vero, Human Embryonic Kidney HEK 293T and neuroblastoma SH-SY5Y cells. Quantitative RT-PCR shows that the level of viral RNA is higher with HS-2015-BA-01 than with PLCal_ZV in two cell lines, but similar in a neuroblastoma cell line. The two strains have 13 amino acids polymorphisms and we analyzed their predicted protein secondary structure. The increased cytopathicity and RNA accumulation of the Brazilian ZIKV isolate compared to the Thai isolate could contribute to the increased pathogenicity observed during the Brazilian epidemic.
Background + Objectives
The echinocandins, amphotericin B preparations, voriconazole and fluconazole are approved for the treatment of invasive candidiasis, though it remains unclear which agent is most effective. In order to answer this question, we performed a systematic review and network meta‐analysis of the randomised controlled trials (RCTs) which evaluated these agents in comparison.
Methods
Four electronic databases were searched from database inception to 8 October 2020. RCTs comparing triazoles, echinocandins or amphotericin B for the treatment of invasive candidiasis or candidemia were included. Random effect Bayesian network meta‐analysis methods were used to compare treatment outcomes.
Results
Thirteen RCTs met inclusion criteria. Of the 3528 patients included from these trials, 1531 were randomised to receive an echinocandin, 944 to amphotericin B and 1053 to a triazole. For all forms of invasive candidiasis, echinocandins were associated with the highest rate of treatment success when compared to amphotericin B (OR 1.41, 95% CI 1.04–1.92) and the triazoles (OR 1.82, 95% CI 1.35–2.51). Rank probability analysis favoured echinocandins as the most effective choice 98% of the time. Overall survival did not significantly differ between groups.
Conclusions
Among patients with invasive candidiasis, echinocandins had the best clinical outcomes and should remain the first‐line agents in the treatment of invasive candidiasis.
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Highlights
CT-based radiomics with machine learning classifier is able to accurately predict primary refractory Diffuse Large B Cell Lymphomas (DLBCL).
The radiomics model exhibits a better discrimination for refractory DLBCL identification compared to available standard clinical criteria.
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