We present the results of a prospective multicenter study of risk factors, etiology, clinical features, and treatment outcomes for mucormycosis in patients with COVID-19 (COVID-M) in the Russian Federation.The study included 60 adult patients with COVID-M. To analyze risk factors for COVID-M, we conducted a case-control study. The control group included 60 adult patients with COVID-19 without mucormycosis. To analyze the clinical manifestations of COVID-M, we created a control group of hematological patients with mucormycosis examined in 2011–2020.In patients with COVID-19, the risk of developing mucormycosis was significantly increased with diabetes mellitus (OR=49) and overweight (OR=4,75), as well as with the use of high (≥100 mg per day for prednisolone) doses of glucocorticosteroids (OR= 4,762), especially ≥10 days (OR=25,4). The main localization of mucormycosis in patients with COVID-19 was the paranasal sinuses (95%) and the orbit (68%). Involvement of ≥2 organs was identified in 70% of patients. The main causative agents of mucormycosis were Rhizopus arrhizus (43%) and unidentified mucormycetes (36%).90-days overall survival of patients with mucormycosis and COVID-19 – 71%. The stay in the ICU (p=0,01), the use of mechanical ventilation (p=0,0481), the presence of CVC (p=0,049), CNS damage (p=0,016) and ≥ 2 organs (p=0,048) significantly worsened the prognosis of the disease. The best prognosis was in patients who received antifungal therapy (p=0,03875) and surgical treatment (p=0,046).
During last years the frequency of invasive pulmonary aspergillosis (IPA) in immunocompetent patients has increased. Clinical case report of successful treatment invasive aspergillosis with influenza A(H1N1) presented in the article. We analyzed the special literature of patients with IPA following influenza infection. The timely identification and treatment of these patients are necessary.
Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and Methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male – 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male – 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male – 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104–11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177–18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.
Objective. To study risk factors, etiology, clinical signs and treatment outcomes of invasive aspergillosis (IA) and mucormycosis combination (IAM) in children. Materials and Methods. A retrospective review of Saint-Petersburg register (1998–2021) of patients with IA was done and children with IAM were included. EORTC/MSGERG 2019 criteria were used for diagnosing and treatment results evaluation of invasive mycosis. We presented a clinical case of IAM in a child with acute lymphoblastic leukemia relapse. Results. A total of 12 children with IAM were included. They accounted 8% of all pediatric patients with invasive aspergillosis (n = 152). IAM was diagnosed in children with hematological malignancies and solid tumors from 4 to 16 years (median age – 11.5 years), mostly in girls (83%). Main risk factors of IAM were prolonged lymphopenia (75%, median 22 days) and neutropenia (67%, median 30 days) due to chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. The predominant etiological agents of IA were Aspergillus niger (33%), A. nidulans (33%) and A. fumigatus (17%), of mucormycosis – Lichtheimia corymbifera (50%) and Rhizomucor spp. (50%). Based on EORTC/MSGERG 2019 criteria, «proven» mucormycosis was diagnosed in 83% of patients, «probable» – in 17%. «Probable» IA was found in 100% of patients. The most common clinical sites of IAM were the lungs (75%) and paranasal sinuses (43%), multifocal involvement was revealed in 33% of patients. Mucormycosis developed during antifungal therapy of IA in 83% of patients. Antifungal therapy of mucormycosis received 75% of patients (amphotericin B lipid complex – 89%, posaconazole – 78%, caspofungin – 33%), combined antifungal therapy – 33%, surgery – 50%; combination of surgical and antifungal treatment was used in 42% of patients. The overall 12-week survival was 77.8%. The use of combined surgical and antifungal treatment significantly improved the survival of children with IAM (p = 0.023). Conclusions. Mucormycosis was diagnosed in 8% of children with IA. IAM developed mostly in patients with hematological malignancies (83%), prolonged lymphopenia (75%) and neutropenia (67%) against the background of chemotherapy, systemic corticosteroids and/or immunosuppressive therapy, as well as HSCT. In 83% of patients mucormycosis was diagnosed during antifungal therapy for IA. The development of IAM increased overall 12-week mortality (50%). The combination of antifungal therapy with surgical treatment significantly improved prognosis of IAM (p = 0.023).
Background:The cause of hepatitis B virus (HBV) reactivation in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) is unclear. Aims: Taiwan has a high prevalence of HBV infection, and this study aimed to investigate the epidemiology of HBV reactivation in patients with CML treated with TKIs. Methods: We retrospectively reviewed 175 adult patients with CML who were treated using TKIs at National Taiwan University Hospital between January 2008 and July 2018. HBV infection status and reactivation were reviewed during follow-up. Results: A total of 99 men and 76 women with a median age of 46 years (range: 18-97) were enrolled in this study. Twenty-one (12%) of 175 patients were carrying HBV when they were diagnosed with CML. Eight HBV carriers were prophylactically treated using an antiviral agent, and the others were closely followed-up. At a median follow-up period of 41 months (range 1-129 months), 6 (28.6%) of the 21 HBV carriers had 7 episodes of HBV reactivation. Two (1.3%) of the 154 negative hepatitis B surface antigen (HBsAg) patients had reverse seroconversion and became positive HBsAg, and both patients had acute blastic transformation and allogeneic transplantation. A univariate analysis revealed positive HBsAg and negative anti-Hepatitis B surface antibodies (anti-HBs Ab) significantly correlated with HBV reactivation. In this retrospective cohort study, the incidence of HBV reactivation was 0.5 per 100 person-years in patients with CML carrying HBV who had been treated with TKIs and 0.076 per 100 person-years in all patients with CML treated with TKIs. Summary/Conclusion: HBV reactivation could develop in patients with CML treated with TKI, especially in those who are HBV carriers. The incidence is lower than it is in hematological patients with HBV carrier status who have been treated with chemotherapy, immunotherapy and stem cell transplantation. We suggest that all patients with CML with positive HBsAg undergo prophylaxis with an antiviral agent. The cause of HBV reactivation in patients with resolved HBV infection and no allogeneic transplantation is unclear, and although the risk is low, further investigation is required.
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