Transcription factor 7-like 2 gene polymorphism and type 2 diabetes mellitus: A meta-analysis

The meta-analysis aimed to investigate transcription factor 7-like 2 (TCF7 L2) (rs12255372 and rs7903146) gene polymorphisms and its association with type 2 diabetes mellitus (T2DM) in a Caucasian and Asian population. The studies included in this article were obtained using online databases. We searched databases such as Scopus, Web of Science, Embase, and PubMed for case–control articles related to TCF7 L2 polymorphisms and T2DM. To determine TCF7 L2 polymorphisms are significantly associated with T2DM, Metagenyo was used to calculate the odds ratio and 95% confidence interval. A total of 15 articles were included in this meta-analysis. TCF7 L2 rs12255372 and rs7903146 gene polymorphisms were strongly related to susceptibility to T2DM in the general population, as shown by the results of a meta-analysis. Subgroup analysis showed that both Asians and Caucasians showed a statistically significant result. This meta-analysis findings supported that TCF7 L2 rs12255372 and rs7903146 gene polymorphisms to determine susceptibility with type 2 diabetes. According to the findings of this study, people with TCF7 L2 gene polymorphisms rs12255372 for allelic, recessive, dominant, and over-dominant models have been connected to T2DM; however, rs7903146 for allelic, recessive, dominant, and over-dominant models have not been associated to the disease

Multi-centre Observational Study on Epidemiology, Treatment, and Outcome of Mucormycosis in India

Background: Though the rise in number of mucormycosis cases has been reported globally, the rise in India is alarming especially in uncontrolled diabetics. However, multiple gaps exist in the understanding of the disease in this country. Methods: To describe the epidemiology, diagnosis, treatment practices, and outcome of mucormycosis in India. A single-arm prospective observational study was conducted in the network of 17 tertiary care centres across India during April 2016 through September 2017. All consecutive proven mucormycosis patients were enrolled in this study. Clinical data including risk factors, investigations, and treatment were collected. All isolates and histopathological specimens were sent to Mycology Reference Laboratory at Chandigarh for final identification (phenotypic and sequencing) and drug susceptibility testing. Results: A total of 474 cases were enrolled between the study period. Rhino-orbito-cerebral mucormycosis was common (42.7%) presentation with 22.8% patients had brain involvement, followed by pulmonary (14.6%), cutaneous (11.8%), isolated renal (3.9%), and intra-abdominal (2.8%) mucormycosis. The underlying disease or predisposing factors were noted in 79.7% cases (84.9% diabetes mellitus, 12.9% steroids, 10.3% trauma or history of surgery, 9.7% malignancy, and 9.2% transplant). The most common agents isolated were Rhizopus species (75.9%, R. arrhizus [74.3%] and R. homothallicus [6.7%]) followed by Apophysomyces variabilis (7.4%), Mucor species (6%), and Lichtheimia corymbifera (4%). The patients were managed by medical therapy in 82.8%, surgery in 56.8% while 51.7% received combined medical and surgical management. Amphotericin B (96.8%) either lipid formulations (65.7%) or conventional form (39.1%) was the common antifungal used. The mortality of patients was 30.4%; of which, 80.3% patients died within 6 weeks of their diagnosis. 24.3% patients left hospital against medical advice while 50.1% survived. Conclusion: Rhino-orbital-cerebral mucormysosis in uncontrolled diabetics is common presentation in India. R. arrhizus followed by A. variabilis are common species isolated from those patients. Survival was noted only in half of the patients despite increased awareness and diagnosis

Multi-centre Observational Study on Epidemiology, Treatment, and Outcome of Mucormycosis in India

Background: Though the rise in number of mucormycosis cases has been reported globally, the rise in India is alarming especially in uncontrolled diabetics. However, multiple gaps exist in the understanding of the disease in this country. Methods: To describe the epidemiology, diagnosis, treatment practices, and outcome of mucormycosis in India. A single-arm prospective observational study was conducted in the network of 17 tertiary care centres across India during April 2016 through September 2017. All consecutive proven mucormycosis patients were enrolled in this study. Clinical data including risk factors, investigations, and treatment were collected. All isolates and histopathological specimens were sent to Mycology Reference Laboratory at Chandigarh for final identification (phenotypic and sequencing) and drug susceptibility testing. Results: A total of 474 cases were enrolled between the study period. Rhino-orbito-cerebral mucormycosis was common (42.7%) presentation with 22.8% patients had brain involvement, followed by pulmonary (14.6%), cutaneous (11.8%), isolated renal (3.9%), and intra-abdominal (2.8%) mucormycosis. The underlying disease or predisposing factors were noted in 79.7% cases (84.9% diabetes mellitus, 12.9% steroids, 10.3% trauma or history of surgery, 9.7% malignancy, and 9.2% transplant). The most common agents isolated were Rhizopus species (75.9%, R. arrhizus [74.3%] and R. homothallicus [6.7%]) followed by Apophysomyces variabilis (7.4%), Mucor species (6%), and Lichtheimia corymbifera (4%). The patients were managed by medical therapy in 82.8%, surgery in 56.8% while 51.7% received combined medical and surgical management. Amphotericin B (96.8%) either lipid formulations (65.7%) or conventional form (39.1%) was the common antifungal used. The mortality of patients was 30.4%; of which, 80.3% patients died within 6 weeks of their diagnosis. 24.3% patients left hospital against medical advice while 50.1% survived. Conclusion: Rhino-orbital-cerebral mucormysosis in uncontrolled diabetics is common presentation in India. R. arrhizus followed by A. variabilis are common species isolated from those patients. Survival was noted only in half of the patients despite increased awareness and diagnosis

Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study

BackgroundFungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. ObjectiveThe primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. MethodsThis multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. ResultsThese Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. ConclusionsFungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. International Registered Report Identifier (IRRID)DERR1-10.2196/5467

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and &lt;70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.</p

Multicenter Case–Control Study of COVID-19–Associated Mucormycosis Outbreak, India

We performed a case–control study across 25 hospitals in India for the period of January–June 2021 to evaluate the reasons for an COVID-19–associated mucormycosis (CAM) outbreak. We investigated whether COVID-19 treatment practices (glucocorticoids, zinc, tocilizumab, and others) were associated with CAM. We included 1,733 cases of CAM and 3,911 age-matched COVID-19 controls. We found cumulative glucocorticoid dose (odds ratio [OR] 1.006, 95% CI 1.004–1.007) and zinc supplementation (OR 2.76, 95% CI 2.24–3.40), along with elevated C-reactive protein (OR 1.004, 95% CI 1.002–1.006), host factors (renal transplantation [OR 7.58, 95% CI 3.31–17.40], diabetes mellitus [OR 6.72, 95% CI 5.45–8.28], diabetic ketoacidosis during COVID-19 [OR 4.41, 95% CI 2.03–9.60]), and rural residence (OR 2.88, 95% CI 2.12–3.79), significantly associated with CAM. Mortality rate at 12 weeks was 32.2% (473/1,471). We emphasize the judicious use of COVID-19 therapies and optimal glycemic control to prevent CAM