COVID‐19‐associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, basic epidemiological characteristics have not been well established. In this systematic review and meta‐analysis, we aimed to determine the incidence and mortality of CAPA in critically ill patients with COVID‐19 to improve guidance on surveillance and prognostication. Observational studies reporting COVID‐19‐associated pulmonary aspergillosis were searched with PubMed and Embase databases, followed by an additional manual search in April 2021. We performed a one‐group meta‐analysis on the incidence and mortality of CAPA using a random‐effect model. We identified 28 observational studies with a total of 3148 patients to be included in the meta‐analysis. Among the 28 studies, 23 were conducted in Europe, two in Mexico and one each in China, Pakistan and the United States. Routine screening for secondary fungal infection was employed in 13 studies. The modified AspICU algorithm was utilised in 15 studies and was the most commonly used case definition and diagnostic algorithm for pulmonary aspergillosis. The incidence and mortality of CAPA in the ICU were estimated to be 10.2% (95% CI, 8.0–12.5; I2 = 82.0%) and 54.9% (95% CI, 45.6–64.2; I2 = 62.7%), respectively. In conclusion, our estimates may be utilised as a basis for surveillance of CAPA and prognostication in the ICU. Large, prospective cohort studies based on the new case definitions of CAPA are warranted to validate our estimates.
Background The value of follow-up blood cultures (FUBCs) to document clearance of bacteremia due to Gram-negative bacilli (GNB) has not been well established. Although previous studies suggested that the yield of FUBCs for GNB bacteremia is low, it remains to be elucidated for whom FUBC may be beneficial and for whom it is unnecessary. Methods A retrospective cohort study was performed at 4 acute care hospitals to identify risk factors for positive FUBCs with GNB bacteremia and to better guide clinicians’ decisions as to which patients may or may not benefit from FUBCs. Participants included adult patients with GNB bacteremia who had FUBCs and were admitted between January 2017 and December 2018. The primary outcomes were the factors associated with positive FUBCs and the yield of FUBCs with and without the factors. Results Of 306 patients with GNB bacteremia who had FUBCs, 9.2% (95% confidence interval, 6.2%–13.0%) had the same GNB in FUBCs. In the multivariate logistic regression analysis, end-stage renal disease on hemodialysis, intravascular device, and bacteremia due to extended-spectrum β-lactamase or carbapenemase-producing organism were identified as independent predictors of positive FUBCs with GNB bacteremia. Approximately 7 FUBCs and 30 FUBCs were needed for patients with ≥1 or no risk factors, respectively, to yield 1 positive result. SummaryThis multi-site retrospective cohort study found that among patients with gram-negative bacilli (GNB) bacteremia, having ESRD on hemodialysis, intravascular devices, or bacteremia due to multi-drug resistant GNB were each independently associated with having a positive follow-up blood culture. Conclusions Follow-up blood culture may not be necessary for all patients with GNB bacteremia and has the highest yield in patients with 1 or more risk factors.
Background Critically ill patients with coronavirus disease‐2019 (COVID‐19) are at the theoretical risk of invasive pulmonary aspergillosis (IPA) due to known risk factors. Patients/Methods We aimed to describe the clinical features of COVID‐19‐associated pulmonary aspergillosis at a single centre in New York City. We performed a retrospective chart review of all patients with COVID‐19 with Aspergillus isolated from respiratory cultures. Results A total of seven patients with COVID‐19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified, all of whom were mechanically ventilated in the ICU. Four patients were classified as putative IPA. The median age was 79 years, and all patients were male. The patients had been mechanically ventilated for a mean of 6.8 days (range: 1‐14 days) before Aspergillus isolation. Serum galactomannan level was positive for only one patient. The majority of our cases received much higher doses of glucocorticoids than the dosage with a proven mortality benefit. All four patients died. Conclusions Vigilance for secondary fungal infections will be needed to reduce adverse outcomes in critically ill patients with COVID‐19.
Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.
The recent increase of COVID-19-associated mucormycosis (CAM) has been commanding global attention. However, basic epidemiologic characteristics have not firmly been established. In this systematic review and meta-analysis, we sought to determine the clinical manifestations, potential risk factors, and outcomes of CAM. Observational studies reporting CAM were searched with PubMed and EMBASE databases in January 2022. We collected data on comorbidities and treatment for COVID-19, and performed a one-group meta-analysis on the frequency of orbital exenteration procedure and mortality of CAM using a random-effect model. Fifty-one observational studies, including a total of 2,312 patients with proven CAM, were identified. Among the 51 studies, 37 were conducted in India, 8 in Egypt, and 6 in other countries. The most common comorbidity was diabetes mellitus (82%). While 57% required oxygenation, 77% received systemic corticosteroids. Among CAM, 97% were rhino-orbital-cerebral (ROCM), and 2.7% were pulmonary mucormycosis. Usual presentations were headache (54%), periorbital swelling/pain (53%), facial swelling/pain (43%), ophthalmoplegia (42%), proptosis (41%), and nasal discharge/congestion (36%). Regarding the outcomes, orbital exenteration was performed in 17% (95% CI: 12–21%, I 2 = 83%) of the COVID-19-associated ROCM patients. The mortality of CAM was 29% (95% CI; 22–36%, I 2 = 92%). In conclusion, this systematic review and meta-analysis indicated that the most prevalent type of CAM was ROCM, and most CAM patients had diabetes mellitus and received systemic glucocorticoids. Clinicians in the endemic areas should have a high index of suspicion for this invasive fungal complication of COVID-19 when a diabetic patient who received high-dose systemic glucocorticoids developed rhino-orbital symptoms.
Insect odorant-binding proteins (OBPs) are thought to play a crucial role in the chemosensation of hydrophobic molecules such as pheromones and host chemicals. The onion fly, Delia antiqua, is a specialist feeder of Allium plants, and utilizes a host odorant n-dipropyl disulfide as a cue for its oviposition. Because n-dipropyl disulfide is a highly hydrophobic compound, some OBPs might be indispensable for perception of it. However, no OBP gene has been identified in D. antiqua. Here, to obtain the DNA sequences of D. antiqua OBPs, we performed an analysis of antennal expressed sequence tags (ESTs). Among 288 EST clones, eight D. antiqua OBP genes were identified for the first time. Phylogenetic analysis revealed that each D. antiqua OBP gene is more closely related to its Drosophila orthologs than to the other D. antiqua OBP genes, suggesting that these OBP genes had emerged before the divergence of Delia and Drosophila species. All of the eight D. antiqua OBPs are expressed not only in the antennae but also in the legs, suggesting additional roles in the taste perception of non-volatile compounds. These findings serve as an important basis for understanding the molecular mechanisms underlying the host adaptations of D. antiqua.
Objective: It remains unclear whether a follow-up blood culture (FUBC) for gram-negative bacilli (GNB) bacteremia should be routinely or selectively performed. To evaluate the value of the practice, we analyzed the association between current FUBC practices and length of stay, antibiotic treatment duration, and in-hospital mortality. Design: Retrospective cohort study. Setting: The study was conducted in 4 acute-care hospitals in New York City. Patients: The study included hospitalized adults with GNB bacteremia between 2017 and 2018. Methods: An FUBC was defined as a blood culture performed between 24 hours and 7 days after an initial blood culture positive for GNB. Using propensity scores for FUBCs performed, patients were matched 1:1 for outcome comparison. Results: In total, 376 hospitalized adults with GNB bacteremia met eligibility criteria. Among them, FUBCs were performed in 271 patients (72%). After propensity score matching, we analyzed 87 pairs of patients with and without an FUBC to compare outcomes. The median length of stay was longer among patients with FUBCs than patients without FUBCs (9 days vs 7 days; P = .017). The median duration of antibiotic treatment was also longer among patients with FUBCs than patients without FUBCs (8 vs 6 days; P = .007). No statistically significant difference was observed in in-hospital mortality between patients with and without an FUBC (odds ratio, 0.37; 95% confidence interval, 0.08–1.36). Conclusions: Current FUBC practices for GNB bacteremia were associated with prolonged length of stay and duration of antibiotic treatment. Further data to better inform selectivity criteria for FUBCs in GNB bacteremia are needed.
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