Description of cryptococcosis following SARS-COV-2 infection: A disease survey through the Mycosis Study Group Education and Research Consortium (MSG-19)

BACKGROUND: Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes. METHODS: We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap survey without personal identifiers. RESULTS: Sixty-nine cases were identified and submitted by 29 separate institutional sites. Cryptococcosis was diagnosed a median of 22 days (interquartile range, 9-42 days) after SARS-CoV-2 infection. Mortality among those with available follow-up was 72% (26/36) for the immunocompetent group and 48% (15/31) for the immunocompromised group (likelihood ratio, 4.01; P = .045). We observed a correlation between disease manifestation (central nervous system infection, proven/probable disseminated disease, and respiratory) and mortality (P = .002). CONCLUSIONS: The mortality rate of 59% for patients with cryptococcosis following SARS-CoV-2 is higher than that of modern Cryptococcus cohorts. There was an association between immunocompromised status and cryptococcal disease manifestations as well as mortality. Moreover, our series emphasizes the need for clinical and laboratory assessment of opportunistic infections beyond 30 days when concerning symptoms develop

Left ventricular trabeculations in cardiac MRI: reference ranges and association with cardiovascular risk factors in UK Biobank

Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (β = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (β = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (β = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7–8.5 g) for men and 4.6 g (IQR, 3.4–6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8–8.7 g) at age 45–50 years to 5.9 g (IQR, 4.3–7.8 g) at age 71–80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established

Hope on the horizon: Novel fungal treatments in development

The treatment of invasive fungal infections remains challenging due to limitations in currently available antifungal therapies including toxicity, interactions, restricted routes of administration, and drug resistance. This review focuses on novel therapies in clinical development, including drugs and a device. These drugs have novel mechanisms of action to overcome resistance, and some offer new formulations providing distinct advantages over current therapies to improve safety profiles and reduce interactions. Among agents that target the cell wall, 2 glucan synthesis inhibitors are discussed (rezafungin and ibrexafungerp), as well as fosmanogepix and nikkomycin Z. Agents that target the cell membrane include 3 fourth-generation azoles, oral encochleated amphotericin B, and aureobasidin A. Among agents with intracellular targets, we will review olorofim, VL-2397, T-2307, AR-12, and MGCD290. In addition, we will describe neurapheresis, a device used as adjunctive therapy for cryptococcosis. With a field full of novel treatments for fungal infections, the future looks promising

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis

BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients. METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 and 35 post enrollment; comparisons used proportional odds ratios. Harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator. The data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. RESULTS: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We did not find evidence of a difference in COVID-19 ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and found no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). CONCLUSIONS: The findings of this individual participant data meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients

Anaesthesiology trainees and their needs: a Romanian perspective. Results from a European survey

Anaesthesiology training is going through continuous transformations worldwide. Recent data from a European Survey on anaesthesiology postgraduate trainees and their concerns have been published for the first time, following an initiative by the European Society of Anaesthesiology. Among the responders of this survey, 10.8% were represented by Romanian trainees. The main needs of the Romanian anaesthesiology trainees who completed the questionnaire were, in descending order educational contents/EDAIC, technical skills, exchange programmes, residency workload, residency costs and autonomy transition. Another observation coming from the analysed data is that Romanian anaesthesiologists in training are highly concerned and interested in the field of intensive care medicine. The results also pinpoint to the high costs associated with continuous medical education, leading to a high incentive for workforce migration.info:eu-repo/semantics/publishedVersio

Performance of the lateral flow assay and the latex agglutination serum cryptococcal antigen test in cryptococcal disease in patients with and without HIV

Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed in 227 patients with cryptococcosis. Of 141 HIV-negative patients, 107 had LA testing and 34 had LFA testing. In patients with disseminated disease, serum CrAg sensitivity by LA was 78.1% compared to 82.6% for LFA. In patients with localized pulmonary disease, serum CrAg sensitivity was 23.5% compared to 90.9% for LFA. Of 86 people living with HIV (PLWH), 76 had LA testing, and 10 had LFA testing. Serum CrAg sensitivity for LA was 94.7% compared to 100% for LFA in patients with disseminated disease. We noted a significant improvement in sensitivity from LA testing to LFA testing, predominantly in those with localized pulmonary disease. However, both LFA and LA appear to be less sensitive in HIV-negative patients than previously described in PLWH

Creation and internal validation of a clinical predictive model for fluconazole resistance in patients with Candida bloodstream infection

BACKGROUND: Fluconazole is recommended as first-line therapy for candidemia when risk of fluconazole resistance (fluc-R) is low. Lack of methods to estimate resistance risk results in extended use of echinocandins and prolonged hospitalization. This study aimed to develop a clinical predictive model to identify patients at low risk for fluc-R where initial or early step-down fluconazole would be appropriate. METHODS: Retrospective analysis of hospitalized adult patients with positive blood culture for RESULTS: We identified 539 adults with candidemia and 72 CONCLUSIONS: This model is a potential tool for identifying patients at low risk for fluc-R candidemia to receive first-line or early step-down fluconazole

Estimating the effects of race and social vulnerability on hospital admission and mortality from COVID-19

OBJECTIVE: To estimate the risk of hospital admission and mortality from COVID-19 to patients and measure the association of race and area-level social vulnerability with those outcomes. MATERIALS AND METHODS: Using patient records collected at a multisite hospital system from April 2020 to October 2020, the risk of hospital admission and the risk of mortality were estimated for patients who tested positive for COVID-19 and were admitted to the hospital for COVID-19, respectively, using generalized estimating equations while controlling for patient race, patient area-level social vulnerability, and time course of the pandemic. RESULTS: Black individuals were 3.57 as likely (95% CI, 3.18-4.00) to be hospitalized than White people, and patients living in the most disadvantaged areas were 2.61 times as likely (95% CI, 2.26-3.02) to be hospitalized than those living in the least disadvantaged areas. While Black patients had lower raw mortality than White patients, mortality was similar after controlling for comorbidities and social vulnerability. DISCUSSION: Our findings point to potent correlates of race and socioeconomic status, including resource distribution, employment, and shared living spaces, that may be associated with inequitable burden of disease across patients of different races. CONCLUSIONS: Public health and policy interventions should address these social factors when responding to the next pandemic

Long-term mortality after Histoplasma infection in people with HIV

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death \u3c 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART

Management of histoplasmosis by infectious disease physicians

BACKGROUND: The Infectious Diseases Society of America (IDSA) guidelines for the management of histoplasmosis were last revised 15 years ago. Since those guidelines were compiled, new antifungal treatment options have been developed. Furthermore, the ongoing development of immunomodulatory therapies has increased the population at increased risk to develop histoplasmosis. METHODS: An electronic survey about the management practices of histoplasmosis was distributed to the adult infectious disease (ID) physician members of the IDSA\u27s Emerging Infections Network. RESULTS: The survey response rate was 37% (551/1477). Only 46% (253/551) of respondents reported seeing patients with histoplasmosis. Regions considered endemic had 82% (158/193) of physicians report seeing patients with histoplasmosis compared to 27% (95/358) of physicians in regions not classically considered endemic ( CONCLUSIONS: Though there are increased reports of histoplasmosis diagnoses outside regions classically considered endemic, a majority of ID physicians reported not seeing patients with histoplasmosis. Most respondents reported adherence to IDSA guidelines recommending itraconazole in each clinical situation. New histoplasmosis guidelines need to reflect the growing need for updated general guidance, particularly for immunocompromised populations