Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal St...Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.展开更多
With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are im...With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions.Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities,a major portion of these patients continue to be affected by post-transplant infections.Of these,fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose.This mini-review aims to discuss the incidence of fungal infections following liver transplantation,the different fungi involved,the risk factors,which predispose these patients to such infections,associated diagnostic challenges,and the role of prophylaxis.The population at risk is increasingly old and frail,suffering from various other co-morbid conditions,and needs special attention.To improve care and to decrease the burden of such infections,we need to identify the at-risk population with more robust clinical and diagnostic parameters.A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.展开更多
The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analy...The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analyze the frequency of invasive fungal infections in people living with HIV. In most studies evaluated, <em>Pneumocystis</em> pneumonia was the most frequent invasive fungal infection among people living with HIV, and cryptococcosis was the second most frequent. Invasive fungal infections are associated with greater morbidity and mortality in people living with HIV. The most important highlighted information is that the lack of epidemiological data on fungal infections in the studied populations was reported by most studies. Therefore, there is a need for further studies to assess the frequency of invasive fungal infection in people living with HIV, which may serve as subsidies for the implementation of strategies for the prevention and management, with a consequent increase in the quality of life and reduction of morbidity/mortality in this population.展开更多
This study aimed to analyze the clinical efficacy and safety of itraconazole. We investigated 68 patients with invasive fungal infections(IFI) in emergency intensive care unit(EICU). A retrospective analysis was p...This study aimed to analyze the clinical efficacy and safety of itraconazole. We investigated 68 patients with invasive fungal infections(IFI) in emergency intensive care unit(EICU). A retrospective analysis was performed in patients with IFI who were treated in the authors' institution, a grade III first class hospital in Beijing, China, between Feb. 2013 and Feb. 2015. The age of patients ranged from 35 to 90 years old with the mean age of(75.1±11.1) years old. The study population comprised 36 male and 32 female patients. Total response rate was 60.3%. The response rates in definitive diagnosis, clinical diagnosis and presumed diagnosis were 33.3%, 59.5% and 65.2%, respectively(P〈0.05). The empirical treatment should be provided for patients with presumed diagnosis as earlier as possible. Eleven(16.2%) cases had adverse drug event(ADE) during treatment. The main signs were hepatic functional impairment and hypokalemia of ADE. The clinical efficacy and safety of intravenous itraconazole were precisely assessed. To reduce the adverse drug reaction(ADR), hepatic and renal function and other biochemical criterion should be closely monitored.展开更多
Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for t...Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.展开更多
Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB).However,these studies have a modest sample size and convey inconclusive results.The ai...Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB).However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections (IFIs),compared with L-AmB.Methods Electronic databases (up to July 31,2013) PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks (RRs) and 95% confidence intervals (C/s).Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat (MITT) patients.The results showed that caspofungin produced equal efficacy in favorable overall response (RR=1.02,95% Cl 0.88-1.18; P=0.81) and mortality rate (RR=1.53,95% Cl 0.38-6.27,P=0.55),safer in clinical adverse events (RR=0.20,95% Cl 0.08-0.54; P=0.001),laboratory adverse events (RR=0.69,95% Cl 0.57-0.84; P=0.0002),and discontinuation rate (RR=0.26,95% Cl 0.08-0.83,P=0.02),compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.展开更多
There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are als...There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are also involved.Candida infections are mostly reported,but patients may also develop infections secondary to non-Candida fungi,especially Aspergillus.Diagnosis and management of these infections is challenging and may involve multiple surgical interventions and prolonged antifungal therapy.Despite this,these infections are associated with high morbidity and mortality.This review described the clinical features,risk factors,and therapeutic interventions required to manage fungal arthritis.展开更多
Objective To summarize the recent findings on the epidemiology of medically important, opportunistic invasive fungal infections (IFIs) in China and discuss the relevant social, economical reasons and medical factors...Objective To summarize the recent findings on the epidemiology of medically important, opportunistic invasive fungal infections (IFIs) in China and discuss the relevant social, economical reasons and medical factors. Data sources We performed a comprehensive search of both English and Chinese literatures of opportunistic IFIs from China up to April 2012. Study selection Relevant literatures involving researches and cases/case sedes were identified, retrieved and reviewed. Results The incidence of opportunistic IFIs in China was steadily increasing. The incidence and mortality of IFIs were different in patients with various underlying conditions/diseases, from 4.12% to 41.18% and 9.8% to 60.0%, respectively. Candida species, Aspergillus species and Cryptococcus neoformans species complex were the most frequent isolated pathogens. Other uncommon opportunistic IFIs were also been reported, including trichosporonosis, mucormycosis, hyalohyphomycosis (hyaline hyphomycetes) and phaeohyphomycosis (dematiaceous hyphomycetes). Reports of Chinese patients differed from those of many other countries as there were a higher number of patients without identifiable underlying diseases/conditions. Conclusions Because of the rapid economic development, changing population structure and a growing number of immunocompromised hosts with risk factors, today opportunistic IFIs in China have a significant impact on public health, associated with high morbidity/mortality and higher care costs. Now information related to the epidemiology of opportunistic IFIs in China is still sparse, so we need more organized groups of clinical scientists performing related researches to help the clinicians to obtain more accurate epidemiological characteristics.展开更多
Background The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study ...Background The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high-resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT. Methods Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis (n=52), candidiasis (n=19) and cryptococcosis (n=14) groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality. Results Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k 〉0.75). There was a significant difference in occurrence ratio of mass among the three groups (P=-0.02). Occurrence ratio of mass (43.3%, 13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%, 2/10; 14.3%, 1/7). There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation. Conclusions The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.展开更多
As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with m...As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.展开更多
Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be...Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be necessary to improve the survival outcomes of these patients.The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.Methods:A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.Results:Nineteen acute leukemia patients,median age 46 years(range 19–65),underwent 20 surgical procedures as management for IFI.Three patients had proven IFI diagnoses prior to surgery.Sixteen patients underwent surgery for both diagnostic and therapeutic purposes.Post-surgery,the diagnostic yield for proven IFI increased by a factor of 5,and 15 patients had definitive IFI diagnoses.Surgical complications included 2 pleural effusions,4 pneumothoraxes,and 1 hydropneumothorax.The median duration of hospitalization for patients with complications was 9 days(range 3–64).Thirteen patients benefited overall from the procedure,3 had temporary clinical benefits,and 2 had progression of IFI.After surgery,the 3-month and 2-year overall survival rates were 89.5%and 57.9%,respectively.The median time from surgery to resumption of chemotherapy or HSCT was 25 days.Conclusions:Surgical interventions for IFI are feasible in selected leukemia patients,as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk,thereby allowing patients to proceed with curative chemotherapy and HSCT.展开更多
BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmona...BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmonary fungal infection has been reported yet.CASE SUMMARY We report the case of a neonate who presented pulmonary fungal infection along with the non-specific features of MMA.Exome sequencing revealed a c.331C>T variant in exon 3 of MMACHC from the father,and a c.658-c.660delAAG variant in exon 4 from the mother,which confirmed the diagnosis of cblC type MMA combined with hyperhomocysteinemia.CONCLUSION Invasive fungal infection might occur in some infants with MMA.Therefore,early diagnosis is recommended for unexplained pulmonary infection.展开更多
Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or p...Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or plaque type.Associated constitutional symptoms are rarely found.The histological presentation may yield a pathognomonic feature,the Medlar(sclerotic)bodies,in which a typical brown to black pigment is depicted,explaining“copper pennies”as its alias.In this article,the case of a 56-year-old woman in the countryside of Brazil is reported,whose main complaint was a chronic leg ulcer for the past 8 years.The left leg had a large,partially ulcerated plaque lesion was found.Microbiological cultures were positive for the pathogen.Histological analysis demonstrated pseudoepitheliomatous hyperplasia,lymphohistiocytic infiltrate and sclerotic bodies(“copper pennies”).CBM’s epidemiological panorama,once established uniquely by geographical distribution,is transitioning to a global health issue,influenced by immunosuppressive conditions,global warming and migration.This scenario demands CBM to be widely considered as a differential diagnosis and may represent a clinical challenge in regions whose professionals have little expertise in infectious tropical diseases.展开更多
Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi effectively.Exploring the im...Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi effectively.Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections.Methods:The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics,fluorescence quantitative PCR,and Western blotting.We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration,pathway enrichment,and differentiation during Candida albicans infection.Results:Our findings indicate that infiltration of CD4^(+)naive cells,regulatory T(Treg)cells,and Microtubules(MT)-associated cells increased after infection,along with impaired T cell activity.Notably,CD4^(+)T cells and plasma cells were enhanced after infection,suggesting that antibody production is dependent on T cells.In addition,we screened 6 hub genes,transcription factor forkhead box protein 3(Foxp3),cytotoxic T-lymphocyte associated protein 4(CTLA4),Interleukin 2 Receptor Subunit Beta(Il2rb),Cd28,C-C Motif Chemokine Ligand 5(Ccl5),and Cd27 for alterations associated with CD4^(+)T cell differentiation.Conclusions:These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.展开更多
Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk...Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.展开更多
AIM:To identify factors related to serious postoperative bacterial and fungal infections in the first 3 mo after living donor liver transplantation(LDLT).METHODS:In the present study,the data of 207 patients from 2004...AIM:To identify factors related to serious postoperative bacterial and fungal infections in the first 3 mo after living donor liver transplantation(LDLT).METHODS:In the present study,the data of 207 patients from 2004 to 2011 were reviewed.The pre-,intra-and post-operative factors were statistically analyzed.All transplantations were approved by the ethics committee of West China Hospital,Sichuan University.Patients with definitely preoperative infections and infections within 48 h after transplantation were excluded from current study.All potential risk factors were analyzed using univariate analyses.Factors significant at a P < 0.10 in the univariate analyses were involved in the multivariate analyses.The diagnostic accuracy of the identified risk factors was evaluated using receiver operating curve.RESULTS:The serious bacterial and fungal infection rates were 14.01% and 4.35% respectively.Enterococcus faecium was the predominant bacterial pathogen,whereas Candida albicans was the most common fungal pathogen.Lung was the most common infection site for both bacterial and fungal infections.Recipient age older than 45 years,preoperative hyponatremia,intensive care unit stay longer than 9 d,postoperative bile leak and severe hyperglycemia were independent risk factors for postoperative bacterial infection.Massive red blood cells transfusion and postoperative bacterial infection may be related to postoperative fungal infection.CONCLUSION:Predictive risk factors for bacterial and fungal infections were indentified in current study.Pre-,intra-and post-operative factors can cause postoperative bacterial and fungal infections after LDLT.展开更多
Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest pa...Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.展开更多
This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)i...This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.展开更多
AIM: To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS: A total of 209 patients(209 eyes) with fungal keratitis, involving no more t...AIM: To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS: A total of 209 patients(209 eyes) with fungal keratitis, involving no more than 50% of the stromal depth and not responding to antifungal agents for 2 wk, were recruited in this retrospective, noncomparative study. The patients were treated with modified corneal ulcer debridement. All visible corneal infiltrates were removed under an operating microscope to obtain a clean stromal bed and smooth incised edges. Antifungal drugs were used immediately after surgery. Healing time of the ulcers was recorded. Fungal recurrence, visual acuity, corneal thickness and risk factors for treatment failure were monitored.RESULTS: The follow-up was 13.6±5.8m o. The corneal ulcers healed in 195 of 209 eyes(93.3%), with a mean healing time of 8.4±6.8 d. The other 14 eyes were further treated by penetrating keratoplasty(PK)(1 eye), anterior lamellar keratoplasty(LK)(7 eyes), conjunctival flap covering(4 eyes) or amniotic membrane transplantation(2 eyes). The best corrected visual acuity(BCVA) was ≥20/70 in 80.3% of the eyes, ≥20/40 in 56.9% of the eyes, and ≥20/25 in 27.3% of the eyes. The corneas at the lesions became thinner, but all in the safe range. No fungal recurrence or corneal ectasis developed during the follow-up. The risk of treatment failure was higher in patients with preoperative hypopyon(P=0.036) and ever using steroid(P=0.025).CONCLUSION: Modified surgical debridement is a simple and effective method for the treatment of superficial fungal infection of the cornea, with improved visual acuity and no recurrence. Such an intervention in time can rapidly control fungal infection and largely shorten corneal ulcer healing time.展开更多
文摘Background: Antifungal resistance (AFR) is a global public health problem with devastating effects, especially among immunocompromised individuals. Addressing AFR requires a One Health approach including Antifungal Stewardship (AFS). This study aimed to comprehensively review global studies published on fungal infections and AFR and to recommend solutions to address this growing problem. Materials and Methods: This was a narrative review that was conducted using published papers on fungal infections, AFR, and AFS between January 1961 and March 2024. The literature was searched using PubMed, Google Scholar, Web of Science, and EMBASE. Results: This found that there has been an increase in fungal infections globally, especially among immunocompromised patients. Due to this increase in fungal infections, there has been a proportionate increase in the use of antifungal agents to prevent and treat fungal infections. This increased use of antifungal agents has worsened the problem of AFR contributing to increased morbidity and mortality. Globally, fungal infections have contributed to 150 million infections annually and 1.7 million deaths per year. By the year 2023, over 3.8 million people died from fungal infections. Addressing AFR remains a challenge because the treatment of antifungal-resistant infections is difficult. Finally, the treatment of fungal infections is a global challenge exacerbated by the limited number of antifungal agents to treat invasive fungal infections. Conclusion: The results of this study indicated that fungal infections and AFR are prevalent across humans, animals, agriculture, and the environment. Addressing this problem requires the provision of solutions such as improving the awareness of AFR, conducting further research on the discovery of new antifungal agents, and implementing AFS programs. If this global problem is not addressed, the morbidity and mortality associated with AFR will continue to rise in the future.
文摘With increasing morbidity and mortality from chronic liver disease and acute liver failure,the need for liver transplantation is on the rise.Most of these patients are extremely vulnerable to infections as they are immune-compromised and have other chronic co-morbid conditions.Despite the recent advances in practice and improvement in diagnostic surveillance and treatment modalities,a major portion of these patients continue to be affected by post-transplant infections.Of these,fungal infections are particularly notorious given their vague and insidious onset and are very challenging to diagnose.This mini-review aims to discuss the incidence of fungal infections following liver transplantation,the different fungi involved,the risk factors,which predispose these patients to such infections,associated diagnostic challenges,and the role of prophylaxis.The population at risk is increasingly old and frail,suffering from various other co-morbid conditions,and needs special attention.To improve care and to decrease the burden of such infections,we need to identify the at-risk population with more robust clinical and diagnostic parameters.A more robust global consensus and stringent guidelines are needed to fight against resistant microbes and maintain the longevity of current antimicrobial therapies.
文摘The increased incidence of invasive and opportunistic mycoses is probably related to the growth of the immunocompromised population, such as people living with HIV. This study is a literature review that aims to analyze the frequency of invasive fungal infections in people living with HIV. In most studies evaluated, <em>Pneumocystis</em> pneumonia was the most frequent invasive fungal infection among people living with HIV, and cryptococcosis was the second most frequent. Invasive fungal infections are associated with greater morbidity and mortality in people living with HIV. The most important highlighted information is that the lack of epidemiological data on fungal infections in the studied populations was reported by most studies. Therefore, there is a need for further studies to assess the frequency of invasive fungal infection in people living with HIV, which may serve as subsidies for the implementation of strategies for the prevention and management, with a consequent increase in the quality of life and reduction of morbidity/mortality in this population.
文摘This study aimed to analyze the clinical efficacy and safety of itraconazole. We investigated 68 patients with invasive fungal infections(IFI) in emergency intensive care unit(EICU). A retrospective analysis was performed in patients with IFI who were treated in the authors' institution, a grade III first class hospital in Beijing, China, between Feb. 2013 and Feb. 2015. The age of patients ranged from 35 to 90 years old with the mean age of(75.1±11.1) years old. The study population comprised 36 male and 32 female patients. Total response rate was 60.3%. The response rates in definitive diagnosis, clinical diagnosis and presumed diagnosis were 33.3%, 59.5% and 65.2%, respectively(P〈0.05). The empirical treatment should be provided for patients with presumed diagnosis as earlier as possible. Eleven(16.2%) cases had adverse drug event(ADE) during treatment. The main signs were hepatic functional impairment and hypokalemia of ADE. The clinical efficacy and safety of intravenous itraconazole were precisely assessed. To reduce the adverse drug reaction(ADR), hepatic and renal function and other biochemical criterion should be closely monitored.
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the China Pharmaceutical University+3 种基金the Shanghai Science and Technology Committee(No.19430741500)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010593)the Fundamental Research Funds for Central Universities(No.20ykpy111,China)
文摘Invasive fungal infections(IFIs)represent a growing public concern for clinicians to manage in many medical settings,with substantial associated morbidities and mortalities.Among many current therapeutic options for the treatment of IFIs,amphotericin B(AmB)is the most frequently used drug.AmB is considered as a first-line drug in the clinic that has strong antifungal activity and less resistance.In this review,we summarized the most promising research efforts on nanocarriers for AmB delivery and highlighted their efficacy and safety for treating IFIs.We have also discussed the mechanism of actions of AmB,rationale for treating IFIs,and recent advances in formulating AmB for clinical use.Finally,this review discusses some practical considerations and provides recommendations for future studies in applying AmB for combating IFIs.
文摘Background Nowadays,there are published trials in regards to the comparison of caspofungin with liposomal amphotericin B (L-AmB).However,these studies have a modest sample size and convey inconclusive results.The aim of this study was to review the efficacy and safety of caspofungin for the treatment of invasive fungal infections (IFIs),compared with L-AmB.Methods Electronic databases (up to July 31,2013) PubMed and Embase databases,the Cochrane Library,and Google Scholar were searched to identify relevant trials of caspofungin and L-AmB.Analyses of efficacy and adverse outcomes were performed by relative risks (RRs) and 95% confidence intervals (C/s).Heterogeneity was assessed by x2-test and the/2-statistic.Results Three trials were included in this meta-analysis with 1249 modified intention-to-treat (MITT) patients.The results showed that caspofungin produced equal efficacy in favorable overall response (RR=1.02,95% Cl 0.88-1.18; P=0.81) and mortality rate (RR=1.53,95% Cl 0.38-6.27,P=0.55),safer in clinical adverse events (RR=0.20,95% Cl 0.08-0.54; P=0.001),laboratory adverse events (RR=0.69,95% Cl 0.57-0.84; P=0.0002),and discontinuation rate (RR=0.26,95% Cl 0.08-0.83,P=0.02),compared with L-AmB in the treatment of patients with IFls.Conclusion Based on the results of this meta-analysis,it would appear that caspofungin was measured to have equal efficacy in clinical outcomes and safer in terms of adverse events.
文摘There has been an increasing incidence of fungal infections in recent years.Rarely joints are also affected by fungal infections.Mainly,these infections develop in prosthetic joints,but sometimes native joints are also involved.Candida infections are mostly reported,but patients may also develop infections secondary to non-Candida fungi,especially Aspergillus.Diagnosis and management of these infections is challenging and may involve multiple surgical interventions and prolonged antifungal therapy.Despite this,these infections are associated with high morbidity and mortality.This review described the clinical features,risk factors,and therapeutic interventions required to manage fungal arthritis.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 31050014) and Academicion Consulting Projects from Chinese Academy of Engineering (No. 2012xy22).
文摘Objective To summarize the recent findings on the epidemiology of medically important, opportunistic invasive fungal infections (IFIs) in China and discuss the relevant social, economical reasons and medical factors. Data sources We performed a comprehensive search of both English and Chinese literatures of opportunistic IFIs from China up to April 2012. Study selection Relevant literatures involving researches and cases/case sedes were identified, retrieved and reviewed. Results The incidence of opportunistic IFIs in China was steadily increasing. The incidence and mortality of IFIs were different in patients with various underlying conditions/diseases, from 4.12% to 41.18% and 9.8% to 60.0%, respectively. Candida species, Aspergillus species and Cryptococcus neoformans species complex were the most frequent isolated pathogens. Other uncommon opportunistic IFIs were also been reported, including trichosporonosis, mucormycosis, hyalohyphomycosis (hyaline hyphomycetes) and phaeohyphomycosis (dematiaceous hyphomycetes). Reports of Chinese patients differed from those of many other countries as there were a higher number of patients without identifiable underlying diseases/conditions. Conclusions Because of the rapid economic development, changing population structure and a growing number of immunocompromised hosts with risk factors, today opportunistic IFIs in China have a significant impact on public health, associated with high morbidity/mortality and higher care costs. Now information related to the epidemiology of opportunistic IFIs in China is still sparse, so we need more organized groups of clinical scientists performing related researches to help the clinicians to obtain more accurate epidemiological characteristics.
文摘Background The correct diagnosis of etiology of fungal infection after bone marrow transplantation is very important to the choice of antifungal drugs and a premise for improvement of therapeutic efficacy. This study aimed to compare high-resolution computed tomography (HRCT) findings of the pulmonary fungal infections to determine whether the etiology of various fungal infections could be diagnosed with HRCT. Methods Eighty-five cases were enrolled. According to the pathogens responsible for fungal infections, the patients were classified into three groups including invasive aspergillosis (n=52), candidiasis (n=19) and cryptococcosis (n=14) groups. All the patients underwent HRCT scans. Two independent radiologists retrospectively analyzed the HRCT scans regarding CT patterns and distribution of lung abnormality. Results Most fungal infections in the three groups occurred in the neutropenic phase. There was no significant difference in the constituent ratio of fungal infections at different phases after bone marrow transplantation among the three groups. Agreement between the two observers for all the CT characteristics of fungal infections was excellent (k 〉0.75). There was a significant difference in occurrence ratio of mass among the three groups (P=-0.02). Occurrence ratio of mass (43.3%, 13/30) in the group with invasive aspergillosis was higher than in each of other two groups (20.0%, 2/10; 14.3%, 1/7). There was no significant difference in other CT characteristics of nodules or masses; including number, margin, halo sign, cavitation and air-crescent sign. There was no significant difference in number, margin, air bronchogram and distribution of air-space consolidation. Conclusions The HRCT appearance of various pulmonary fungal infections has a great deal of overlap and is nonspecific. Mass is more common in invasive aspergillosis, which is helpful to the diagnosis of invasive aspergillosis after bone marrow transplantation.
基金supported by the National Natural Science Foundation of China(No.82073789,and 81673376)the project for Innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006,China)+1 种基金Chongqing Postgraduate Research and Innovation Project(CYB20106,China)CAS Interdiscipliary Innovation Team(China)。
文摘As a typical human pathogenic fungus,Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing w700,000 deaths annually.Cryptococcosis is not just an infection with multi-organ involvement,intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C.neoformans infections.Because adequate accumulation of drugs at target organs and cells is still difficult to achieve,an effective delivery strategy is desperately required to treat these infections.Here,we report a bioresponsive micro-to-nano(MTN)system that effectively clears the C.neoformans in vivo.This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3(MMP-3)in infectious microenvironments(IMEs)and secreted protein acidic and rich in cysteine(SPARC)in several associated target cells.In this MTN system,bovine serum albumin(BSA,a natural ligand of SPARC)was used for the preparation of nanoparticles(NPs),and then microspheres were constructed by conjugation with a special linker,which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide.This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection,and then hydrolyzed into BSA NPs by MMP-3 in the IMEs.The NPs further targeted the lung tissue,brain and infected macrophages based on the overexpression of SPARC,reaching multiple targets and achieving efficient treatment.We have developed a size-tunable strategy where microspheres"shrink"to NPs in IMEs,which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.
文摘Objectives:Invasive fungal infections(IFIs)are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation(HSCT).Surgical interventions may be necessary to improve the survival outcomes of these patients.The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.Methods:A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.Results:Nineteen acute leukemia patients,median age 46 years(range 19–65),underwent 20 surgical procedures as management for IFI.Three patients had proven IFI diagnoses prior to surgery.Sixteen patients underwent surgery for both diagnostic and therapeutic purposes.Post-surgery,the diagnostic yield for proven IFI increased by a factor of 5,and 15 patients had definitive IFI diagnoses.Surgical complications included 2 pleural effusions,4 pneumothoraxes,and 1 hydropneumothorax.The median duration of hospitalization for patients with complications was 9 days(range 3–64).Thirteen patients benefited overall from the procedure,3 had temporary clinical benefits,and 2 had progression of IFI.After surgery,the 3-month and 2-year overall survival rates were 89.5%and 57.9%,respectively.The median time from surgery to resumption of chemotherapy or HSCT was 25 days.Conclusions:Surgical interventions for IFI are feasible in selected leukemia patients,as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk,thereby allowing patients to proceed with curative chemotherapy and HSCT.
文摘BACKGROUND Methylmalonic acidemia(MMA)is characterized by non-specific symptoms such as vomiting,and feeding difficulties,along with delayed mental and physical development.However,no case of MMA combined with pulmonary fungal infection has been reported yet.CASE SUMMARY We report the case of a neonate who presented pulmonary fungal infection along with the non-specific features of MMA.Exome sequencing revealed a c.331C>T variant in exon 3 of MMACHC from the father,and a c.658-c.660delAAG variant in exon 4 from the mother,which confirmed the diagnosis of cblC type MMA combined with hyperhomocysteinemia.CONCLUSION Invasive fungal infection might occur in some infants with MMA.Therefore,early diagnosis is recommended for unexplained pulmonary infection.
文摘Chromoblastomycosis(CBM)is a fungal disease,distributed in tropical and subtropical regions,affecting mainly rural workers.It is characterized by chronic skin lesions that may vary from nodular,tumorous,verrucous or plaque type.Associated constitutional symptoms are rarely found.The histological presentation may yield a pathognomonic feature,the Medlar(sclerotic)bodies,in which a typical brown to black pigment is depicted,explaining“copper pennies”as its alias.In this article,the case of a 56-year-old woman in the countryside of Brazil is reported,whose main complaint was a chronic leg ulcer for the past 8 years.The left leg had a large,partially ulcerated plaque lesion was found.Microbiological cultures were positive for the pathogen.Histological analysis demonstrated pseudoepitheliomatous hyperplasia,lymphohistiocytic infiltrate and sclerotic bodies(“copper pennies”).CBM’s epidemiological panorama,once established uniquely by geographical distribution,is transitioning to a global health issue,influenced by immunosuppressive conditions,global warming and migration.This scenario demands CBM to be widely considered as a differential diagnosis and may represent a clinical challenge in regions whose professionals have little expertise in infectious tropical diseases.
基金supported by National Key Research and Development Program of China(2021YFC2301405)Chongqing Talent Program(No.CQYC202003220).
文摘Objective:Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms,including coordinated innate and adaptive immune responses,to neutralize invading fungi effectively.Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections.Methods:The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics,fluorescence quantitative PCR,and Western blotting.We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration,pathway enrichment,and differentiation during Candida albicans infection.Results:Our findings indicate that infiltration of CD4^(+)naive cells,regulatory T(Treg)cells,and Microtubules(MT)-associated cells increased after infection,along with impaired T cell activity.Notably,CD4^(+)T cells and plasma cells were enhanced after infection,suggesting that antibody production is dependent on T cells.In addition,we screened 6 hub genes,transcription factor forkhead box protein 3(Foxp3),cytotoxic T-lymphocyte associated protein 4(CTLA4),Interleukin 2 Receptor Subunit Beta(Il2rb),Cd28,C-C Motif Chemokine Ligand 5(Ccl5),and Cd27 for alterations associated with CD4^(+)T cell differentiation.Conclusions:These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.
基金supported by the National Natural Science Foundation of China(82373808)Chongqing Natural Science Foundation(cstc2021jcyj-bshX0125)+1 种基金Fundamental Research Funds for the Central Universities(SWURC2020001)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006).
文摘Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.
基金Supported by The National Science and Technology Major Project of China,No.2012ZX10002-016 and 2012ZX10002017-006
文摘AIM:To identify factors related to serious postoperative bacterial and fungal infections in the first 3 mo after living donor liver transplantation(LDLT).METHODS:In the present study,the data of 207 patients from 2004 to 2011 were reviewed.The pre-,intra-and post-operative factors were statistically analyzed.All transplantations were approved by the ethics committee of West China Hospital,Sichuan University.Patients with definitely preoperative infections and infections within 48 h after transplantation were excluded from current study.All potential risk factors were analyzed using univariate analyses.Factors significant at a P < 0.10 in the univariate analyses were involved in the multivariate analyses.The diagnostic accuracy of the identified risk factors was evaluated using receiver operating curve.RESULTS:The serious bacterial and fungal infection rates were 14.01% and 4.35% respectively.Enterococcus faecium was the predominant bacterial pathogen,whereas Candida albicans was the most common fungal pathogen.Lung was the most common infection site for both bacterial and fungal infections.Recipient age older than 45 years,preoperative hyponatremia,intensive care unit stay longer than 9 d,postoperative bile leak and severe hyperglycemia were independent risk factors for postoperative bacterial infection.Massive red blood cells transfusion and postoperative bacterial infection may be related to postoperative fungal infection.CONCLUSION:Predictive risk factors for bacterial and fungal infections were indentified in current study.Pre-,intra-and post-operative factors can cause postoperative bacterial and fungal infections after LDLT.
文摘Invasive infections are a major complication before liver transplantation(LT)and in the early phase after surgery.There has been an increasing prevalence of invasive fungal disease(IFD),especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure,who suffer from a profound state of immune dysfunction and receive intensive care management.In such patients,who are listed for LT,development of an IFD often worsens hepatic and extra-hepatic organ dysfunction,requiring a careful evaluation before surgery.In the post-transplant setting,the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis,even if several major issues still remain,such as duration,target population and drug type(s).Nevertheless,the development of IFD in the early phase after surgery significantly impairs graft and patient survival.This review outlines presentation,prophylactic and therapeutic strategies,and outcomes of IFD in LT candidates and recipients,providing specific considerations for clinical practice.
基金the National Natural Science Foundation of China(No.81500105).
文摘This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1(Dectin-1),Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),and myeloid differentiation primary response 88(MyDHH)influence the susceptibility to pulmonary invasive fungal disease(IFD)in patients with acute myeloid leukemia(AML)from a Chinese Han population.Eight single nucleotide polymorphisms(SNPs)of Dectin-1(rs 16910526,rs3901533,and rs7309123),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)and MyD88(rs4988453 and rs4988457)in the genomic DNA of 172 adult AML patients were genotyped.Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)consensus guidelines.SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD.The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR(qRT-PCR),and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed.Two Dectin-1 intron SNPs(rs3901533 and rs7309123)were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population.Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model(G/T+G/G vs.T/T,OR:2.158;95%Cl:1.109-4.2,P=0.02),Dectin-1 rs3901533 G allele(OR:2.201;95%Cl:1.206-4.019,P=0.01),or Dectin-1 rs7309123 C allele(OR:1.919;95%Cl:1.047-3.518,P=0.03).There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs(rs 16910526),TLR2(rs5743708),TLR4(rs4986790 and rs4986791)or MyDHH(rs4988453 and rs4988457).In conclusion,two Dectin-1 SNPs(rs3901533 and rs7309123)are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.
基金Supported by the Natural Science Foundation of Shandong Province(No.ZR2014HQ059)
文摘AIM: To evaluate the efficacy of modified corneal ulcer debridement in superficial fungal keratitis unresponsive to medications.METHODS: A total of 209 patients(209 eyes) with fungal keratitis, involving no more than 50% of the stromal depth and not responding to antifungal agents for 2 wk, were recruited in this retrospective, noncomparative study. The patients were treated with modified corneal ulcer debridement. All visible corneal infiltrates were removed under an operating microscope to obtain a clean stromal bed and smooth incised edges. Antifungal drugs were used immediately after surgery. Healing time of the ulcers was recorded. Fungal recurrence, visual acuity, corneal thickness and risk factors for treatment failure were monitored.RESULTS: The follow-up was 13.6±5.8m o. The corneal ulcers healed in 195 of 209 eyes(93.3%), with a mean healing time of 8.4±6.8 d. The other 14 eyes were further treated by penetrating keratoplasty(PK)(1 eye), anterior lamellar keratoplasty(LK)(7 eyes), conjunctival flap covering(4 eyes) or amniotic membrane transplantation(2 eyes). The best corrected visual acuity(BCVA) was ≥20/70 in 80.3% of the eyes, ≥20/40 in 56.9% of the eyes, and ≥20/25 in 27.3% of the eyes. The corneas at the lesions became thinner, but all in the safe range. No fungal recurrence or corneal ectasis developed during the follow-up. The risk of treatment failure was higher in patients with preoperative hypopyon(P=0.036) and ever using steroid(P=0.025).CONCLUSION: Modified surgical debridement is a simple and effective method for the treatment of superficial fungal infection of the cornea, with improved visual acuity and no recurrence. Such an intervention in time can rapidly control fungal infection and largely shorten corneal ulcer healing time.