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The Journal of Allergy and Clinical... May 2021Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus and impacts 10% of individuals with cystic fibrosis (CF). A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus and impacts 10% of individuals with cystic fibrosis (CF). A diagnosis of ABPA is challenging to establish in CF owing to overlapping clinical and radiologic features with CF lung disease. Recent studies have identified blood tests, imaging, and other biomarkers that may be useful for diagnosis.
OBJECTIVE
To summarize biomarkers that can aid in the diagnosis of ABPA in CF patients and to quantify their diagnostic accuracy through meta-analysis.
METHODS
We searched MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials and included studies that used a laboratory technique or imaging modality in CF patients diagnosed with ABPA. Pooled sensitivity and specificity were calculated using a hierarchical summary receiver operating characteristic model.
RESULTS
We identified 791 articles, of which 29 met our eligibility criteria and 9 were included in the meta-analysis. Hyperattenuating mucus on computed tomography (CT) scan (n = 3 studies; pooled sensitivity 62% and specificity 92%) and serum specific immunoglobulin E against recombinant Aspergillus funigatus antigens f4 (n = 6; 69%, 89%) and f6 (n = 6; 39%, 97%) demonstrated high specificity. Based on single studies, serum thymus and activation regulated chemokine (92%, 94%), stimulated basophil expression of CD203c (94%, 74%), the inverted mucoid impaction signal on magnetic resonance imaging (94%, 100%), and skin prick test with recombinant Aspergillus fumigatus f4 and/or f6 (100%, 100%) showed high sensitivity and specificity.
CONCLUSIONS
Recent studies have found promising biomarkers for diagnosing ABPA in CF. Further research is needed to improve our understanding of their utility in diagnosis and disease monitoring.
Topics: Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Biomarkers; Cystic Fibrosis; Humans; Immunoglobulin E
PubMed: 33454395
DOI: 10.1016/j.jaip.2020.12.064 -
ClinicoEconomics and Outcomes Research... 2021Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and...
INTRODUCTION
Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and invasive mucormycosis (IM) are two of the most common mold infections. A better understanding of patient comorbidities and risk factors that predispose IMI may help clinicians to refine the difficult diagnostic and treatment process.
METHODS
A systematic literature review (SLR) was conducted (January 2008-October 2019) for studies reporting comorbidities/risk factors of patients with IA or IM (Phase I), followed by an analysis on the Optum US EHR database of prominent risk factor cohorts based on SLR findings and expert opinion (Phase II). From the four identified patient cohorts: 1) patients undergoing solid organ transplant (SOT) and patients with 2) hematologic cancers, 3) diabetes, or 4) lung disease, rates of IA, IM, or concurrent IA and IM; patient comorbidities; and Charlson Comorbidity Index (CCI) scores were reported.
RESULTS
The SLR included 88 studies, and 46 were used to select comorbidities/risk factors cohorts in IA and IM patients. The most important comorbidities/risk factors in IA and IM patients were diabetes, lung disease, hematological malignances, and SOT. In the Optum database (N=101,340,454 patients), IA rates were highest in lung transplant (10.81%) patients and IM rates were highest in intestine transplant (0.83%) patients, lung transplant (0.43%), and hematopoietic stem cell transplant (0.49%). CCI scores were elevated in all mold infection groups compared to the total Optum cohort.
CONCLUSION
The current study describes patient comorbidity and risk factors associated with IA and IM. These data can be used to refine clinical decision-making regarding when to suspect mold infections. Future research should focus on identifying whether patients respond differently to various antifungal treatments to determine if strategic recommendations should be made for certain patient groups.
PubMed: 34211287
DOI: 10.2147/CEOR.S308744 -
World Neurosurgery May 2021Cerebral aspergillosis carries a high mortality. Rapid diagnosis and treatment can increase survival, but symptoms and imaging findings are nonspecific. The literature...
OBJECTIVE
Cerebral aspergillosis carries a high mortality. Rapid diagnosis and treatment can increase survival, but symptoms and imaging findings are nonspecific. The literature on cerebral aspergillosis consists mostly of case reports and case series and lacks large-scale review of data.
METHODS
We performed a review of the literature using PubMed in March 2019. We recorded the year of publication, age and sex of patients, neurosurgical involvement, the antifungals administered, use of intrathecal antifungals, and the outcome of patients. The relationships among variables were tested using bivariant statics and linear regression.
RESULTS
A total of 324 studies met the eligibility criteria, and 198 studies including 248 patients were included. Surgical resection (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.25-0.80; P < 0.01) and administration of voriconazole (OR, 0.32; 95% CI, 0.18-0.55; P < 0.001) or itraconazole (OR, 0.36; 95% CI, 0.16-0.72; P < 0.001) were shown to be significantly associated with survival.
CONCLUSIONS
Given the significant survival benefits for patients who received voriconazole and surgical intervention, we suggest early antifungal medical treatment and resection.
Topics: Antifungal Agents; Brain; Brain Diseases; Humans; Neuroaspergillosis; Neurosurgical Procedures; Survival Rate
PubMed: 33482411
DOI: 10.1016/j.wneu.2021.01.033 -
Mycoses Mar 2022Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics.
METHODS
Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782).
RESULTS
Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs.
CONCLUSIONS
FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.
Topics: Acute-On-Chronic Liver Failure; Aspergillosis; Candidiasis, Invasive; Humans; Invasive Fungal Infections; Liver Cirrhosis
PubMed: 34724269
DOI: 10.1111/myc.13387 -
Mycoses Feb 2022An increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta-analysis to estimate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
An increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta-analysis to estimate the incidence, risk factors and outcomes of IPA in patients with influenza.
METHODS
A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases from their inception to 31 August 2021 for eligible studies. Data on the incidence and risk factors of and mortality due to IPA in influenza patients were pooled using a random-effects model. Sensitivity analyses restricted to severe influenza requiring intensive care unit (ICU) support and multiple subgroup analyses were performed.
RESULTS
Fourteen studies involving 6024 hospitalised patients with influenza were included. IPA was estimated to occur in 10% of influenza patients, with a mortality rate of 52%. Similar incidence (11%) and mortality (54%) estimates for IPA were observed in the sensitivity analysis including severe cases requiring ICU support. Subgroup analysis by geographical location showed a similar IPA rate between European (10%) and non-European (11%) studies. The IPA rate in the subset of nine studies using the modified AspICU criteria was 13%. Most subgroup analyses showed ≥50% mortality in IPA patients. Several predictors for IPA susceptibility were identified, including male sex, smoking history, chronic lung disease, influenza A (H1N1), severe conditions requiring supportive therapy, corticosteroid use before admission, solid organ transplant and haematological malignancy.
CONCLUSIONS
The IPA is common in individuals with severe influenza, and the prognosis is particularly poor. Influenza patients, especially those with high-risk factors, should be thoroughly screened for IPA.
Topics: Humans; Incidence; Influenza A Virus, H1N1 Subtype; Influenza, Human; Invasive Pulmonary Aspergillosis; Retrospective Studies; Risk Factors
PubMed: 34882852
DOI: 10.1111/myc.13410 -
Mycoses Sep 2020Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening debilitating lung disease necessitating long-term oral antifungal treatment. However, development... (Meta-Analysis)
Meta-Analysis
Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening debilitating lung disease necessitating long-term oral antifungal treatment. However, development of antifungal-resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single-case reports and case series reporting <10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n = 143) or an echinocandin (n = 237) and were included in the meta-analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI): 52%-70%; I = 73.3%; P < .001), to amphotericin B was 58% (95% CI: 36%-80%; I = 86.6%; P < .001) and to echinocandins was 62% (95% CI: 53%-72%; I = 63.6%; P < .001). Amphotericin B courses were usually doses at slightly <1 mg/Kg (deoxycholate) or 3 mg/Kg (liposomal) for 2-3 weeks. Micafungin doses varied from 12.5 to 300 mg (frequently, 150 mg) daily for at least 3 weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5-35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head-to-head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short- and longer-term outcomes of these agents.
Topics: Administration, Intravenous; Antifungal Agents; Chronic Disease; Disease Management; Echinocandins; Humans; Pulmonary Aspergillosis
PubMed: 32542771
DOI: 10.1111/myc.13131 -
The Lancet. Infectious Diseases Mar 2021Fungal keratitis is a severe corneal infection that often results in blindness and eye loss. The disease is most prevalent in tropical and subtropical climates, and...
Fungal keratitis is a severe corneal infection that often results in blindness and eye loss. The disease is most prevalent in tropical and subtropical climates, and infected individuals are frequently young agricultural workers of low socioeconomic status. Early diagnosis and treatment can preserve vision. Here, we discuss the fungal keratitis diagnostic literature and estimate the global burden through a complete systematic literature review from January, 1946 to July, 2019. An adapted GRADE score was used to evaluate incidence papers-116 studies provided the incidence of fungal keratitis as a proportion of microbial keratitis and 18 provided the incidence in a defined population. We calculated a minimum annual incidence estimate of 1 051 787 cases (736 251-1 367 323), with the highest rates in Asia and Africa. If all culture-negative cases are assumed to be fungal, the annual incidence would be 1 480 916 cases (1 036 641-1 925 191). In three case series, 8-11% of patients had to have the eye removed, which represents an annual loss of 84 143-115 697 eyes. As fungal keratitis probably affects over a million people annually, an inexpensive, simple diagnostic method and affordable treatment are needed in every country.
Topics: Humans; Eye Infections, Fungal; Fungi; Global Health; Incidence; Keratitis; Risk Factors
PubMed: 33645500
DOI: 10.1016/S1473-3099(20)30448-5 -
PloS One 2022This systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran.
OBJECTIVES
This systematic review aims to summarize the mycological and clinical features of COVID-19-associated fungal infections (CAFIs) in Iran.
METHODS
PubMed, Web of Science, Scopus, Cochrane Library, SID, Magiran, IranDoc, and Google Scholar were searched for Persian and English articles published from January 1, 2020, to November 5, 2021, using a systematic search strategy. Studies on Iranian patients suffering from CAFIs were included in the review.
RESULTS
Twenty-two studies comprising 169 patients were retrieved. Reported CAFIs included candidiasis (85, 50.30%), mucormycosis (35, 20.71%), aspergillosis (29, 17.16%), fusariosis (6, 3.55%), three cases caused by rare pathogens (Rhodotorula mucilaginosa, Diaporthe foeniculina, and Sarocladium kiliense) and 11 (6.51%) uncharacterized mold infections. The most common underlying diseases were diabetes (67/168, 39.88%), cardiovascular diseases (55/168, 32.74%), and hypertension (43/168, 25.59%). The use of antibiotics (111/124, 89.52%), corticosteroids (93/132, 70.44%), and mechanical ventilation (66, 51.16%) were the most common predisposing factors. Totally, 72 (50.35%) of 143 patients with CAFIs died (data were not available for 26 patients).
CONCLUSION
Fungal infections are evident to be a complication of COVID-19 in Iran; thus, clinicians should consider them as a differential diagnosis, especially in patients with comorbidities and previous antibiotic or corticosteroid use.
Topics: COVID-19; Diabetes Mellitus; Humans; Iran
PubMed: 35816494
DOI: 10.1371/journal.pone.0271333 -
American Journal of Transplantation :... Feb 2021To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies... (Meta-Analysis)
Meta-Analysis
To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk.
Topics: Aspergillosis; Graft Rejection; Humans; Invasive Fungal Infections; Kidney Transplantation; Risk Factors
PubMed: 32780498
DOI: 10.1111/ajt.16248 -
BMC Infectious Diseases Feb 2024Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the development of IA, as well as the potential implications for risk stratification strategies.
METHODS
We searched National Center for Biotechnology Information (NCBI) databases for publications until October 2023 containing age characteristics of patients with and without IA. A random-effects model with the application of inverse-variance weighting was used to pool reported estimates from each study, and meta-regression and subgroup analyses were utilized to assess sources of heterogeneity.
RESULTS
A systematic review was conducted, resulting in the inclusion of 55 retrospective observational studies with a total of 13,983 patients. Meta-analysis revealed that, on average, patients with IA were approximately two and a half years older (95% Confidence Interval [CI] 1.84-3.31 years; I = 26.1%) than those without the disease (p < 0.0001). No significant moderators could explain the observed heterogeneity in age difference. However, subgroup analysis revealed that age differences were more pronounced within particular patient groups compared to others. For example, patients with and without IA who had primary severe lung infections exhibited a greater difference in mean age than other patient cohorts.
CONCLUSIONS
Further research, such as individual patient data meta-analysis, is necessary to better understand the potential relationship between increasing age and the likelihood of IA. Improved risk stratification strategies based on patient age could potentially enhance the early detection and treatment of IA, ultimately improving patient outcomes.
Topics: Humans; Retrospective Studies; Aspergillosis; Invasive Fungal Infections; Databases, Factual; Probability
PubMed: 38373908
DOI: 10.1186/s12879-024-09109-2