Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis. There are estimated to be in excess of four million patients affected world-wide. The importance of recognizing ABPA relates to the improvement of patient symptoms, and delay in development or prevention of bronchiectasis, one manifestation of permanent lung damage in ABPA. Environmental factors may not be the only pathogenetic factors because not all asthmatics develop ABPA despite being exposed to the same environment. Allergic bronchopulmonary aspergillosis is probably a polygenic disorder, which does not remit completely once expressed, although long-term remissions do occur. In a genetically predisposed individual, inhaled conidia of A. fumigatus germinate into hyphae with release of antigens that activate the innate and adaptive immune responses (Th2 CD4(+) T cell responses) of the lung. The International Society for Human and Animal Mycology (ISHAM) has constituted a working group on ABPA complicating asthma (www.abpaworkinggroup.org), which convened an international conference to summarize the current state of knowledge, and formulate consensus-based guidelines for diagnosis and therapy. New diagnosis and staging criteria for ABPA are proposed. Although a small number of randomized controlled trials have been conducted, long-term management remains poorly studied. Primary therapy consists of oral corticosteroids to control exacerbations, itraconazole as a steroid-sparing agent and optimized asthma therapy. Uncertainties surround the prevention and management of bronchiectasis, chronic pulmonary aspergillosis and aspergilloma as complications, concurrent rhinosinusitis and environmental control. There is need for new oral antifungal agents and immunomodulatory therapy.

Minimal hepatic encephalopathy (MHE) has a negative effect on patients' daily functioning. Thus far, no study has investigated the effect of treatment-related improvement in cognitive functions on health-related quality of life (HRQOL). We measured psychometric performance by number and figure connection tests parts A and B, picture completion, and block design tests and HRQOL by the Sickness Impact Profile (SIP) of 90 patients with cirrhosis on inclusion into the study and 3 months later. A Z score less than ؊2 on the neuropsychological (NP) tests was considered abnormal. Sixty-one (67.7%) patients had MHE. They were randomly assigned in a 1:1 ratio to receive treatment (lactulose) for 3 months (n ‫؍‬ 31) or no treatment (n ‫؍‬ 30) in a nonblinded design. H epatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction diagnosed after exclusion of other known brain diseases. The Working Party at the 11th World Congress of Gastroenterology, Vienna, under the Organization Mondiale de Gastroentrologie proposed a multiaxial definition of HE that defined both the type of hepatic abnormality (type A, B, or C) and the duration and characteristics of neurological manifestations (episodic, persistent, or minimal HE) in chronic liver disease. 1 HE has been considered a continuous dimension that could be measured with 1 index to summarize several neurological domains, such as cognition, emotion, behavior, and biologic rhythms. Minimal hepatic encephalopathy (MHE) represents a portion of this dimension and is the mildest form of HE. Whereas patients with HE have impaired intellectual functioning, personality changes, altered level of consciousness, and neuromuscular dysfunction, patients with MHE have no recognizable clinical symptoms of HE but do have mild cognitive and psychomotor deficits. In the absence of a "gold standard" for determining MHE, neuropsychological (NP) and neurophysiological methods have been the most trusted and widely used tests to diagnose this condition. 1,2 MHE is considered clinically relevant for at least 3 reasons. First, it impairs patients' daily functioning and

S econdary infections are known to complicate the clinical course of coronavirus disease . Bacterial infections are the most common secondary infections, but increasing reports of systemic fungal infections are causing concern. In the early part of the COVID-19 pandemic, <1% of secondary infections reported in COVID-19 patients were fungal (1,2). Preexisting conditions, indiscriminate use of antimicrobial and glucocorticoid drugs, and lapses in infection control practices are putative factors contributing to the emergence of systemic fungal infections in severe COVID-19 cases (3). After incidence of candidemia and invasive aspergillosis in COVID-19 patients increased (4,5), awareness of possible fungal co-infections increased among clinicians and microbiologists. One study reported invasive fungal infections in ≈6% of hospitalized COVID-19 patients (6). Occasional reports of COVID-19-associated mucormycosis (CAM) from various centers (7,8) and a series of 18 cases from a city in South India increased our concerns about CAM (9). India has a high burden of mucormycosis among patients with uncontrolled diabetes mellitus, and many severe COVID-19 patients have diabetes (8,10). India also is one of the countries worst affected by the COVID-19 pandemic. Thus, we would expect India to have many CAM cases. We conducted a nationwide multicenter study to evaluate the epidemiology and outcomes of CAM and compare the results with cases of mucormycosis unrelated to COVID-19 (non-CAM). Methods Study Design and SettingWe conducted a retrospective observational study involving 16 healthcare centers across India (Figure 1).

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19.He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10-14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher

Objectives: To describe the epidemiology, management and outcome of individuals with mucormycosis; and to evaluate the risk factors associated with mortality. Methods: We conducted a prospective observational study involving consecutive individuals with proven mucormycosis across 12 centres from India. The demographic profile, microbiology, predisposing factors, management and 90-day mortality were recorded; risk factors for mortality were analysed. Results: We included 465 patients. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/ 465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the participants. Amphotericin B was the primary therapy in 81.9% (381/465), and posaconazole was used as combination therapy in 53 (11.4%) individuals. Antifungal therapy was inappropriate in 7.6% (30/394) of the individuals. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (versus liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival. Conclusions: Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation. A.