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.

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.

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.

Management of acute cardiovascular events in patients with COVID-19.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the newly discovered virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had been noticed to have high morbidity and mortality. Apart from pneumonia, COVID-19 can also cause damage to the cardiovascular system, and co-occurring with cardiovascular injury leads to a poorer prognosis. Besides, amid the pandemic of COVID-19, the management of critical cardiovascular events needs to further account for the highly infectious coronavirus, prompt and optimal treatments, clinician's safety, and healthcare provider's capacity. This review article aims to provide more comprehensive and appropriate guidance for the management of critical cardiovascular disease, including ST-segment elevation myocardial infarction (STEMI), non-STEMI acute coronary syndrome, cardiogenic shock, acute heart failure, cardiopulmonary resuscitation, and advanced care planning, during the COVID-19 epidemic.

Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections.

BACKGROUND/PURPOSE: Aspergillus-associated infection might comprise up to 23-29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections. METHODS: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. RESULTS: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p < 0.001), with significant odds ratios after adjusting for important variables. The factor of GM index ≥0.6 had a 19.82 (95% CI, 4.91 to 80.07, p < 0.0001) odds of expiring in an ICU among the Aspergillus group. CONCLUSION: Dual Aspergillus and influenza infection is emerging in southern Taiwan. Meanwhile, community-acquired P. aeruginosa should be listed in the common copathogens with severe influenza. The 67% mortality linked to aspergillosis highlights the need for physicians to focus attention on patients with GM ≥ 0.6.

Characterization of IS26-composite transposons and multidrug resistance in conjugative plasmids from Enterobacter cloacae.

SHV-12 is the most widespread resistance determinant of Enterobacter cloacae in Taiwan; however, blaSHV-12 has rarely been mobilized. Six multidrug-resistant E. cloacae isolates were collected. After conjugal transfer, plasmid profiling and analysis of incompatibility groups was performed to characterize the genetic context of blaSHV-12 -containing fragments. The presence of mobile genetic elements was demonstrated by PCR, cloning, sequencing and bioinformatics analyses. Four different ß-lactamase genes (blaTEM-1 , blaSHV-12 , blaCTX-M-3 and/or blaCTX-M-14 ) were observed in the conjugative plasmids belonging to the IncHI2 (n = 4), IncI1 or IncP incompatibility groups. The IS26-blaSHV-12 -IS26 locus was located in five different genetic environments. A novel structural organization of a class 1 integron with the aac(6')-IIc cassette truncated by IS26 was identified in one isolate. Thus, blaSHV-12 was obtained from different plasmids through IS26-mediated homologous recombination. IS26 plays a vital role in the distribution of mobile resistance elements between different plasmids found in multidrug-resistant E. cloacae isolates.

A fish-stunning wound infection with acute cardiac injury.

Vibrio vulnificus typically causes septicemia and necrotic wound infection. Among V vulnificus­related complications, acute nonthrombotic myocardial damage has not been reported. The most effective antibiotic treatment of V vulnificus infection includes combination of a third-generation cephalosporin and a tetracycline or its analogue. However, recommendations of a fourth-generation cephalosporinbased regimen for treating the disease are not established. A 67-year-old diabetic man acquired V vulnificus infection via a fish-stunning wound on the right foot. The patients developed septicemia and hemorrhagic bullous necrotic wounds and followed by acute nonthrombotic cardiac injury with low cardiac output. After initial resuscitation, we applied dobutamine inotropic therapy with combination of cefpirome and ciprofloxacin or minocycline, which achieved a good clinical outcome.

Ceftolozane/tazobactam: Literature review of its activity on Taiwanese isolates before its launch in Taiwan (2012-2021).

Ceftolozane, a novel cephalosporin, combined with tazobactam, a known ß-lactamase inhibitor, shows robust antipseudomonal activity, although it doesn't cover carbapenemases. Our review of data from 2012 to 2021 in Taiwan highlights TOL/TAZ's in-vitro performance. TOL/TAZ is most effective against Pseudomonas aeruginosa (91.3-94.4 % susceptible, with an MIC <4 µg/mL). It also demonstrates good activity against Enterobacterales, including Escherichia coli (88-94.3 % susceptible), Klebsiella pneumoniae (72.6-84.1 % susceptible), Citrobacter koseri (93.3 % susceptible), Klebsiella oxytoca (98.1-100 % susceptible), and Proteus mirabilis (100 % susceptible). However, its efficacy varies among species typically associated with chromosomally-mediated AmpC production, such as Morganella morganii (100 % susceptible), Serratia marcescens (81.3-90.0 % susceptible), Enterobacter cloacae species complex (76.6-76.7 % susceptible), Klebsiella aerogenes (66.7-89.6% susceptible), and Citrobacter freundii (60.0 % susceptible). For carbapenem-nonsusceptible isolates, TOL/TAZ is less effective against K. pneumoniae and E. coli (susceptibility <10 %) but remains useful for P. aeruginosa (susceptibility 81.3-91.8 %). In conclusion, TOL/TAZ shows potent activity against P. aeruginosa and carbapenem-susceptible Enterobacterales in Taiwan.

In vitro efficacies and resistance profiles of rifampin-based combination regimens for biofilm-embedded methicillin-resistant Staphylococcus aureus.

To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline alone or in combination with rifampin against biofilm-embedded MRSA were measured. The rifampin-resistant mutation frequencies were evaluated. Of the rifampin-based combinations, rifampin enhances the antibacterial activities of and even synergizes with fusidic acid, tigecycline, and, to a lesser extent, linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such combinations with weaker rifampin resistance induction activities may provide a therapeutic advantage in MRSA biofilm-related infections.

Gauze versus solid skin barrier for tracheostomy care: a crossover randomized clinical trial.

PURPOSE: The aim of this study was to compare gauze and a solid pectin-based skin barrier to evaluate clinical outcomes and cost-effectiveness of care for tracheostomy wounds. METHODS: A randomized clinical trial with crossover design was conducted to compare gauze to a solid skin barrier for management of patients with tracheostomies. The main study outcomes were skin integrity, dressing change frequency, time required for dressing changes, product costs, and nurses' satisfaction. SETTING AND SUBJECTS: A convenience sample was recruited from 2 medical centers in Taiwan. Using permuted block randomization, patients undergoing tracheostomy were randomly allocated to 1 of 2 groups. One group received tracheostomy care with gauze for the first 6 days and a solid pectin-based skin barrier for the following 6 days. This regimen was reversed in the second group. RESULTS: Skin integrity was significantly better among patients managed with a solid skin barrier as compared to management with gauze (Z=-2.75, P= .006). No significant differences in dressing change frequency, time required for dressing changes, or product costs between the 2 groups were found. Nurses' satisfaction was significantly higher for the solid skin barrier as compared to gauze (Z=-2.31, P= .021, for group 1, and T=-1.97, P= .048, for group 2). CONCLUSIONS: The use of a solid skin barrier for tracheostomy care was associated with lower occurrences of impaired skin integrity and higher satisfaction among nurses when compared to gauze.

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.

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.

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.

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.