Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases

Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.Open access funding provided by Projekt DEA

COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Raquel Sabino was not included as an author in the published article. It was corrected a posteriori.Erratum in - Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? [Front Microbiol. 2018] Front Microbiol. 2019 Jan 14;9:3245. doi: 10.3389/fmicb.2018.03245. eCollection 2018.Disponível em: https://www.frontiersin.org/articles/10.3389/fmicb.2018.03245/fullFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882871/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340063/Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.This work was supported by ECMM, ISHAM, and EFISG and in part by an unrestricted research grant through the Investigator Initiated Studies Programof Astellas, MSD, and Pfizer. This study was fundet by the Christian Doppler Laboratory for invasive fungal infections.info:eu-repo/semantics/publishedVersio

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis

An Estimate of Severe and Chronic Fungal Diseases in the Republic of Kazakhstan

Our work aimed to generate a preliminary estimation of severe and chronic fungal diseases in the Republic of Kazakhstan with a model proposed by LIFE (Leading International Fungal Education). Calculations were carried out on data from 2015. Published results of studies of mycoses in Kazakhstan were identified; in the absence of national data from the scientific literature, the frequency of life-threatening and serious mycoses in defined groups of patients at risk from other countries were taken into account. We also used analogous estimations of mycoses in the Russian Federation. We estimate that 300,824 patients (1.7% of the population) were affected by severe and chronic mycotic diseases. There were an estimated 15,172 cases of acute mycoses, notably tinea capitis in children (11,847), Pneumocystis pneumonia and invasive candidiasis, and 285,652 of chronic fungal diseases. The most frequent were chronic recurrent vulvovaginal candidiasis (273,258 cases) and chronic pulmonary aspergillosis (6231). There is uncertainty about the prevalence of asthma in adults; the official number is 12,478 patients, but a prevalence estimate of 1.47% from a WHO consortium yields a prevalence of ~170,000 affected. We have used the official figures to generate the prevalence of fungal asthma, but it is likely to be a significant underestimate. Conclusion: Results of investigation indicate significant prevalence of severe and chronic mycoses in the Republic of Kazakhstan

An estimate of severe and chronic fungal diseases in the Republic of Kazakhstan

Our work aimed to generate a preliminary estimation of severe and chronic fungal diseases in the Republic of Kazakhstan with a model proposed by LIFE (Leading International Fungal Education). Calculations were carried out on data from 2015. Published results of studies of mycoses in Kazakhstan were identified; in the absence of national data from the scientific literature, the frequency of life-threatening and serious mycoses in defined groups of patients at risk from other countries were taken into account. We also used analogous estimations of mycoses in the Russian Federation. We estimate that 300,824 patients (1.7% of the population) were affected by severe and chronic mycotic diseases. There were an estimated 15,172 cases of acute mycoses, notably tinea capitis in children (11,847), Pneumocystis pneumonia and invasive candidiasis, and 285,652 of chronic fungal diseases. The most frequent were chronic recurrent vulvovaginal candidiasis (273,258 cases) and chronic pulmonary aspergillosis (6231). There is uncertainty about the prevalence of asthma in adults; the official number is 12,478 patients, but a prevalence estimate of 1.47% from a WHO consortium yields a prevalence of ~170,000 affected. We have used the official figures to generate the prevalence of fungal asthma, but it is likely to be a significant underestimate. Conclusion: Results of investigation indicate significant prevalence of severe and chronic mycoses in the Republic of Kazakhstan

Trichosporon 2022

Trichosporon 2022 позволяет определить основные факторы для оптимального лечения инвазивного трихоспороноза. Метод отражает наиболее важные рекомендации современных руководств и позволяет количественно оценить приверженность этим рекомендациям и оптимизировать антифунгальную терапию

The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries

Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19-associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or cerebral involvement. Furthermore, a substantial proportion of patients who survived had life-changing morbidities (eg, loss of vision in 46% of survivors). Our Review indicates that COVID-19-associated mucormycosis is associated with high morbidity and mortality. Diagnosis of pulmonary mucormycosis is particularly challenging, and might be frequently missed in India

Towards Bright Single-Photon Emission in Elliptical Micropillars

In recent years, single-photon sources (SPSs) based on the emission of a single semiconductor quantum dot (QD) have been actively developed. While the purity and indistinguishability of single photons are already close to ideal values, the high brightness of SPSs remains a challenge. The widely used resonant excitation with cross-polarization filtering usually leads to at least a two-fold reduction in the single-photon counts rate, since single-photon emission is usually unpolarized, or its polarization state is close to that of the exciting laser. One of the solutions is the use of polarization-selective microcavities, which allows one to redirect most of the QD emission to a specific polarization determined by the optical mode of the microcavity. In the present work, elliptical micropillars with distributed Bragg reflectors are investigated theoretically and experimentally as a promising design of such polarization-selective microcavities. The impact of ellipticity, ellipse area and verticality of the side walls on the splitting of the optical fundamental mode is investigated. The study of the near-field pattern allows us to detect the presence of higher-order optical modes, which are classified theoretically. The possibility of obtaining strongly polarized single-photon QD radiation associated with the short-wavelength fundamental cavity mode is shown