Aspergillus coinfection in critically Ill patients with severe dengue.

In 2014-2015, a significant outbreak of dengue fever occurred in southern Taiwan, with a subsequent decline in dengue incidence. Despite this, there is emerging concern about virus-associated aspergillosis, yet limited research has explored coinfections involving dengue and aspergillosis. We conducted a retrospective study at a single center in Southern Taiwan, specifically focusing on dengue patients admitted to the intensive care unit during the period between July and November 2015. Among the 142 dengue patients studied, only 8.06 % (10/142) underwent serum galactomannan testing, with a single patient undergoing bronchoalveolar lavage (BAL) galactomannan assay. Out of those tested, 20 % (2/10) returned positive serum galactomannan results. Herein, we present two consecutive cases of coinfection involving dengue and pulmonary aspergillosis in immunocompetent patients.

Characteristics and outcomes for pulmonary aspergillosis in critically ill patients without influenza: A 3-year retrospective study.

BACKGROUND: Previous studies have revealed higher mortality rates in patients of severe influenza coinfected with invasive pulmonary aspergillosis (IPA) than in those without the coinfection; nonetheless, the clinical outcome of IPA in critically ill patients without influenza remains unclear. PATIENTS AND METHODS: This retrospective study was conducted in three institutes. From 2016-2018, all adult patients diagnosed with IPA in the intensive care units (ICUs) were identified. The logistic regression was used to identify the potential risk factors associated with in-hospital mortality in patients with non-influenza IPA. The stratified analysis of IPA patients with and without antifungal therapy was also performed. The final model was established using a forward approach, selecting variables with p-values less than 0.05. RESULTS: Ninety patients were included during the study period, and 63 (70%) were men. The most common comorbidity was diabetes mellitus (n = 24, 27%), followed by solid cancers (n = 22, 24%). Antifungal therapy was administered to 50 (56%) patients, mostly voriconazole (n = 44). The in-hospital mortality rate was 49% (n = 44). Univariate analysis revealed that the risk factors for mortality included daily steroid dose, APACHE II score, SOFA score, C-reactive protein (CRP) level, carbapenem use, antifungal therapy, and caspofungin use. Multiple regression analysis identified four independent risk factors for mortality: age (Odds ratio [OR], 1.052, p = 0.013), daily steroid dose (OR, 1.057, p = 0.002), APACHE II score (OR, 1.094, p = 0.012), and CRP level (OR, 1.007, p = 0.008). Furthermore, the multivariable analysis identified that more physicians would initiate antifungal therapy for patients with prolonged steroid use (p = 0.001), lower white blood cell count (p = 0.021), and higher SOFA score (p = 0.048). Thus, under the selection bias, the independent risk factors for mortality in the antifungal treatment subgroup were daily steroid dose (OR, 1.046, p = 0.001) and CRP (OR, 1.006, p = 0.018), whereas the independent risk factor for mortality in the untreated group became APACHE II score (OR, 1.232, p = 0.007). CONCLUSIONS: Patients with IPA had a substantially high mortality. Overall, age, steroid use, APACHE II score, and CRP level were identified as the independent risk factors for mortality in patients in the ICU.

Isolation of Mycoplasma salivarium in the empyema of a diabetic patient with deep neck infection and necrotizing mediastinitis: A case report.

Mycoplasma species (spp.) are predominantly found in the human oropharynx, and extracavity infections are rare. Conventional culture limitations hinder Mycoplasma spp. recovery, potentially causing overlooked infections. Molecular techniques reveal their roles in various infections. Mycoplasma pneumoniae causes pneumonia, while Mycoplasma salivarium (M. salivarium) in empyema is scarcely reported. We present a case of a 61-year-old man who suffered from tonsillitis, deep neck infection, necrotizing mediastinitis, and bilateral pleural infections. Mixed pathogens, mainly M. salivarium, were implicated.

COVID-19 Associated with Cryptococcosis: A New Challenge during the Pandemic.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a great threat to global health. In addition to SARS-CoV-2 itself, clinicians should be alert to the possible occurrence of co-infection or secondary infection among patients with COVID-19. The possible co-pathogens include bacteria, viruses, and fungi, but COVID-19-associated cryptococcosis is rarely reported. This review provided updated and comprehensive information about this rare clinical entity of COVID-19-associated cryptococcosis. Through an updated literature search till 23 August 2022, we identified a total of 18 culture-confirmed case reports with detailed information. Half (n = 9) of them were elderly. Fifteen (83.3%) of them had severe COVID-19 and ever received systemic corticosteroid. Disseminated infection with cryptococcemia was the most common type of cryptococcosis, followed by pulmonary and meningitis. Except one case of C. laurentii, all other cases are by C. neoformans. Liposomal amphotericin B and fluconazole were the most commonly used antifungal agents. The overall mortality was 61.1% (11/18) and four of them did not receive antifungal agents before death. Improving the poor outcome requires a physician's high suspicion, early diagnosis, and prompt treatment.

Identification of immune and stromal cell infiltration-related gene signature for prognosis prediction in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a common and life-threatening hematologic malignancy, its occurrence and progression are closely related to immune/stromal cell infiltration in the bone marrow (BM) microenvironment. However, no studies have described an immune/stromal cell infiltration-related gene (ISCIRG)-based prognostic signature for ALL. A total of 444 patients involving 437 bulk and 7 single-cell RNA-seq datasets were included in this study. Eligible datasets were searched and reviewed from the database of TCGA, TARGET project and GEO. Then an integrated bioinformatics analysis was performed to select optimal prognosis-related genes from ISCIRGs, construct a nomogram model for predicting prognosis, and assess the predictive power. After LASSO and multivariate Cox regression analyses, a seven ISCIRGs-based signature was proved to be able to significantly stratify patients into high- and low-risk groups in terms of OS. The seven genes were confirmed that directly related to the composition and status of immune/stromal cells in BM microenvironment by analyzing bulk and single-cell RNA-seq datasets. The calibration plot showed that the predicted results of the nomogram were consistent with the actual observation results of training/validation cohort. This study offers a reference for future research regarding the role of ISCIRGs in ALL and the clinical care of patients.

Diagnosis and Treatment of Fungus and Virus Interaction.

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COVID-19 associated mucormycosis - An emerging threat.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly become a global threaten since its emergence in the end of 2019. Moreover, SARS-CoV-2 infection could also present with co-infection or secondary infection by other virus, bacteria, or fungi. Among them, mucormycosis is a rare but aggressive fungal disease and it mainly affects patients particularly with poorly controlled diabetes mellitus with diabetic ketoacidosis (DKA). We here did a comprehensive review of literature reporting COVID-19 associated with mucormycosis (CAM) cases, which have been reported worldwide. The prevalence is higher in India, Iran, and Egypt than other countries, particularly highest in the states of Gujarat and Maharashtra in India. Poor diabetic control and the administration of systemic corticosteroids are the common precipitating factors causing mucormycosis in the severe and critical COVID-19 patients. In addition, COVID-19 itself may affect the immune system resulting in vulnerability of the patients to mucormycosis. Appropriate treatments of CAM include strict glycemic control, extensive surgical debridement, and antifungal therapy with amphotericin B formulations.

Epidemiology of extended-spectrum ß-lactamases in Enterobacterales in Taiwan for over two decades.

The emergence of antimicrobial resistance among microorganisms is a serious public health concern, and extended-spectrum ß-lactamases (ESBL)-producing Enterobacterales is one of the major concerns among antibiotic-resistant bacteria. Although the prevalence of ESBL in Enterobacterales has been increasing with time, the prevalence of ESBL could differ according to the species, hospital allocation, sources of infections, nosocomial or community acquisitions, and geographic regions. Therefore, we conducted a comprehensive review of the epidemiology of ESBL-producing Enterobacterales in Taiwan. Overall, the rates of ESBL producers are higher in northern regions than in other parts of Taiwan. In addition, the genotypes of ESBL vary according to different Enterobacterales. SHV-type ESBLs (SHV-5 and SHV-12) were the major types of Enterobacter cloacae complex, but Serratia marcescens, Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae were more likely to possess CTX-M-type ESBLs (CTX-M-3 and CTX-M-14). Moreover, a clonal sequence type of O25b-ST131 has been emerging among urinary or bloodstream E. coli isolates in the community in Taiwan, and this clone was potentially associated with virulence, ESBL (CTX-M-15) production, ciprofloxacin resistance, and mortality. Finally, the evolution of the genetic traits of the ESBL-producing Enterobacterales isolates helps us confirm the interhospital and intrahospital clonal dissemination in several regions of Taiwan. In conclusion, continuous surveillance in the investigation of ESBL production among Enterobacterales is needed to establish its long-term epidemiology.

The Impacts of Aspergillosis on Outcome, Burden and Risks for Mortality in Influenza Patients with Critical Illness.

Previous studies have revealed higher mortality rates in patients with severe influenza who are coinfected with invasive pulmonary aspergillosis (IPA) than in those without IPA coinfection; nonetheless, the clinical impact of IPA on economic burden and risk factors for mortality in critically ill influenza patients remains undefined. The study was retrospectively conducted in three institutes. From 2016 through 2018, all adult patients with severe influenza admitted to an intensive care unit (ICU) were identified. All patients were classified as group 1, patients with concomitant severe influenza and IPA; group 2, severe influenza patients without IPA; and group 3, severe influenza patients without testing for IPA. Overall, there were 201 patients enrolled, including group 1 (n = 40), group 2 (n = 50), and group 3 (n = 111). Group 1 patients had a significantly higher mortality rate (20/40, 50%) than that of group 2 (6/50, 12%) and group 3 (18/11, 16.2%), p < 0.001. The risk factors for IPA occurrence were solid cancer and prolonged corticosteroid use in ICU of >5 days. Group 1 patients had significantly longer hospital stay and higher medical expenditure than the other two groups. The risk factors for mortality in group 1 patients included patients' Charlson comorbidity index, presenting APACHE II score, and complication of severe acute respiratory distress syndrome. Overall, IPA has a significant adverse impact on the outcome and economic burden of severe influenza patients, who should be promptly managed based on risk host factors for IPA occurrence and mortality risk factors for coinfection with both diseases.

Myocardial Infarction and Azygos Vein Thrombosis After ChAdOx1 nCoV-19 Vaccination in a Hemodialysis Patient.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after vaccination of Oxford-AstraZeneca coronavirus disease 2019 (COVID-19) vaccine (AZD1222) or Janssen COVID-19 vaccine. It makes a rare complication of thrombosis at common and/or uncommon organs with thrombocytopenia after COVID-19 vaccination four to 28 days later and most patients were younger than 60 years of age. We reported the case of a 75-year-old female with end-stage renal disease who received regular hemodialysis. She received Oxford-AstraZeneca COVID-19 vaccination eight days ago and then she suffered from intermittent chest tightness and epigastric pain with tarry stool passage for two days. Severe thrombocytopenia with elevated D-dimer value was noted and computed tomography of the chest showed azygos vein thrombosis. Elevated cardiac enzyme with ST-T change in 12-lead electrocardiogram was also noted. For positive anti-platelet factor 4 antibodies, VITT with myocardial infarction and azygos vein thrombosis was diagnosed.

Clinical Efficacy of Infliximab in Patients With Crohn Disease in Different Locations of Disease Pathology: A Meta-Analysis.

PURPOSE: Infliximab (INX) has been approved for treating Crohn disease (CD) for many years, showing promis-ing efficacy in the clinic. However, the efficacy of the drug and the prognosis of CD vary significantly with dif-ferent locations of disease pathology. This study evaluated the efficacy of INX and prognosis in CD in different locations of disease pathology using systematic meta-analysis. METHODS: We used "Infliximab OR Remicade OR Avakine OR Inflectra OR Renflexis OR Remsima OR IgG1k monoclonal antibody" AND "Crohn's disease OR IBD OR inflammatory bowel disease" as search strategies for searching in PubMed, Wanfang and Embase. A systematic meta-analysis for overall proportions was used to analyze the data. RESULTS: Twelve studies involving 1,978 patients were included. The results confirmed that treatment with INX led to high clinical remission rates (82%, 95% CI: 64%-92%) and low relapse rates (4%, 95% CI: 2%-9%) in patients with CD. Our results also indicated that use of INX in patients with colon only (L2) CD led to lower clinical remission rates, and use of INX in patients with ileum and colon (L3) CD led to higher relapse rates. CONCLUSION: Our findings show different remission rates depending on location of the disease and may be useful for clinicians' choice of therapeutics.

Klebsiella pneumoniae Harboring Carbapenemase Genes in Taiwan: Its Evolution over 20 Years, 1998-2019.

Klebsiella pneumoniae (K. pneumoniae) is an important pathogen causing various types of human infections in Taiwan. Carbapenemases have increasingly been reported in Enterobacterales in the past two decades. Carbapenemase-producing K. pneumoniae (CPKP), a major resistance concern that has emerged during the last decade, has become a global threat, with its related infections associated with high morbidity and mortality; however, therapeutic options for CPKP-associated infections are limited. Carbapenemases - including K. pneumoniae carbapenemases (KPC)-2, New Delhi metallo-ß-lactamase (NDM)-1, Verona integron-encoded metallo-ß-lactamase (VIM)-1, imipenemase (IMP)-1, and oxacillinase (OXA)-48 - have been reported worldwide, with a marked prevalence in different countries or areas of the world. Understanding the epidemiology of carbapenemase producers is important for the prevention of their expansion. This review examined the evolution of CPKP in the last two decades to better understand the role of CPKP in Taiwan. It discovered that the endemicity has changed from IMP-8, NDM-1 and VIM-1 to the most common KPC-2 and rapidly emerging OXA-48. Resistance epidemiology, genetic background, virulence factors, therapy, and outcomes are discussed in this paper.

Epidemiological Correlation of Pulmonary Aspergillus Infections with Ambient Pollutions and Influenza A (H1N1) in Southern Taiwan.

An increase in fungal spores in ambient air is reported during a spike in particulate matter (PM2.5 and PM10) aerosols generated during dust or smog events. However, little is known about the impact of ambient bioaerosols on fungal infections in humans. To identify the correlation between the incidence of pulmonary aspergillosis and PM-associated bioaerosols (PM2.5 and PM10), we retrospectively analyzed data between 2015 and 2018 (first stage) and prospectively analyzed data in 2019 (second stage). Patient data were collected from patients in three medical institutions in Tainan, a city with a population of 1.88 million, located in southern Taiwan. PM data were obtained from the Taiwan Air Quality Monitoring Network. Overall, 544 non-repeated aspergillosis patients (first stage, n = 340; second stage, n = 204) were identified and enrolled for analysis. The trend of aspergillosis significantly increased from 2015 to 2019. Influenza A (H1N1) and ambient PMs (PM2.5 and PM10) levels had significant effects on aspergillosis from 2015 to 2018. However, ambient PMs and influenza A (H1N1) in Tainan were correlated with the occurrence of aspergillosis in 2018 and 2019, respectively. Overall (2015-2019), aspergillosis was significantly correlated with influenza (p = 0.002), influenza A (H1N1) (p < 0.001), and PM2.5 (p = 0.040) in Tainan City. Using a stepwise regression model, influenza A (H1N1) (p < 0.0001) and Tainan PM10 (p = 0.016) could significantly predict the occurrence of aspergillosis in Tainan. PM-related bioaerosols and influenza A (H1N1) contribute to the incidence of pulmonary aspergillosis.

Cefoperazone/sulbactam: New composites against multiresistant gram negative bacteria?

Sulbactam, a class A ß-lactamase inhibitor, added to cefoperazone either at a fixed 8 mg/L level of sulbactam or at a level of fixed cefoperazone: sulbactam ratio (2:1) would constitute a combination form of cefoperazone/sulbactam, which has better activities against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii than cefoperazone alone. Cefoperazone/sulbactam (1:1 or 1:2) has greater in-vitro activity against most multidrug-resistant organisms (ESBL- and AmpC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii except for carbapenem-resistant P. aeruginosa) than a 2:1 ratio. However, increased sulbactam concentration may induce AmpC production. Besides, sulbactam concentration might not be readily achievable in serum if the susceptibility rates were defined by the breakpoints of higher sulbactam composites, such as ≤16/16 (1:1) or 16/32 (1:2) mg/L. Carbapenemases (KPC-, OXA-type enzymes and metallo-ß-lactamases) can't be inhibited by sulbactam. Some in-vitro studies showed that increasing sulbactam composites of cefoperazone/sulbactam had no effect on carbapenem-resistant P. aeruginosa, suggesting the presence of carbapenemases or AmpC overproduction that could not be overcome by increasing sulbactam levels to recover cefoperazone activity. Sulbactam alone has good intrinsic activity against carbapenem-resistant Acinetobacter strains sometimes even in the presence of carbapenemase genes, suggesting unsteady levels of carbapenemases. In conclusion, appropriate composites of cefoperazone and ß-lactamase inhibitor sulbactam may expand the clinical use if the pharmacokinetic optimization could be achieved in the human serum.

Cardiovascular Complications of COVID-19 and Associated Concerns: A Review.

SARS-CoV-2 is the virus that has caused the current coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 is characterized by significantly affecting the cardiovascular system of infected patients. In addition to the direct injuries caused by the virus, the subsequent cytokine storm - an overproduction of immune cells and their activating compounds - also causes damage to the heart. The development of anti-SARS-CoV-2 treatments is necessary to control the epidemic. Despite an explosive growth in research, a comprehensive review of up-to-date information is lacking. Herein, we summarize pivotal findings regarding the epidemiology, complications, and mechanisms of, and recent therapies for, COVID-19, with special focus on its cardiovascular impacts.

A Double-Edged Sword-Cardiovascular Concerns of Potential Anti-COVID-19 Drugs.

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). COVID-19 significantly affects multiple systems including the cardiovascular system. Most importantly, in addition to the direct injury from the virus per se, the subsequent cytokine storm, an overproduction of immune cells and their activating compounds, causes devastating damage. To date, emerging anti-SARS-CoV-2 treatments are warranted to control epidemics. Several candidate drugs have been screened and are currently under investigation. These primarily include antiviral regimens and immunomodulatory regimens. However, beyond the anti-SARS-CoV-2 effects, these drugs may also have risks to the cardiovascular system, especially altering cardiac conduction. Herein, we review the cardiovascular risks of potential anti-COVID-19 drugs.

Cardiac Involvement of COVID-19: A Comprehensive Review.

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2 caused COVID-19 has reached a pandemic level. COVID-19 can significantly affect patients' cardiovascular systems. First, those with COVID-19 and preexisting cardiovascular disease have an increased risk of severe disease and death. Mortality from COVID-19 is strongly associated with cardiovascular disease, diabetes, and hypertension. Second, therapies under investigation for COVID-19 may have cardiovascular side effects of arrhythmia. Third, COVID-19 is associated with multiple direct and indirect cardiovascular complications. Associated with a high inflammatory burden related to cytokine release, COVID-19 can induce vascular inflammation, acute myocardial injury, myocarditis, arrhythmias, venous thromboembolism, metabolic syndrome and Kawasaki disease. Understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for cardiac and/or COVID-19 patients. We hereby review the literature on COVID-19 regarding cardiovascular virus involvement.