Extracorporeal Membrane Oxygenation in Septic Cardiomyopathy Caused by Aspergillus Infection: The First Case Report.

Septic cardiomyopathy (SCM) is often associated with bacterial infections but also occurs with infections with viruses such as influenza and spirochetes, including syphilis. However, there has been no systematic investigation into whether Aspergillus infections can cause septic cardiomyopathy. We report on such a case for the first time in a patient without immunodeficiency. Therefore, clinicians should be concerned with septic cardiomyopathy caused by some atypical or rare pathogens when admitting such patients.

The incidence and impact of atrial fibrillation on hospitalized Coronavirus disease-2019 patients.

BACKGROUND: Since 2019, Coronavirus disease-2019 (COVID-19) has raised unprecedented global health crisis. The incidence and impact of atrial fibrillation (AF) on patients with COVID-19 remain unclearly defined. METHODS: We conducted a retrospective cohort study using ICD-10 codes to identify patients with a primary diagnosis of COVID-19 with or without AF in National Inpatient Sample Database 2020. We compared the outcome of COVID-19 patients with a concurrent diagnosis of AF with those without. HYPOTHESIS: AF will adversely affect the prognosis of hospitalized COVID-19 patients. RESULTS: A total of 211 619 patients with a primary diagnosis of COVID-19 were identified. Among these patients, 31 923 (15.08%) had a secondary diagnosis of AF. Before propensity score matching, COVID-AF cohort was older (75.8 vs. 62.2-year-old, p < .001) and had more men (57.5% vs. 52.0%, p < .001). It is associated with more comorbidities, mainly including diabetes mellitus (43.7% vs. 39.9%, p < .001), hyperlipidemia (54.6% vs. 39.8%, p < .001), chronic kidney disease (34.5% vs. 17.0%, p < .001), coronary artery disease (35.3% vs. 14.4%, p < .001), anemia (27.8% vs. 18.6%, p < .001), and cancer (4.8% vs. 3.4%, p < .001). After performing propensity score match, a total of 31 862 patients were matched within each group. COVID-AF cohort had higher inpatient mortality (22.2% vs. 15.3%, p < .001) and more complications, mainly including cardiac arrest (3.9% vs. 2.3%, p < .001), cardiogenic shock (0.9% vs. 0.3%, p < .001), hemorrhagic stroke (0.4% vs. 0.3%, p = .025), and ischemic stroke (1.3% vs. 0.7%, p < .001). COVID-AF cohort was more costly, with a longer length of stay, and a higher total charge. CONCLUSION: AF is common in patients hospitalized for COVID-19, and is associated with poorer in-hospital mortality, immediate complications and increased healthcare resource utilization.

Cholesterol-induced HRD1 reduction accelerates vascular smooth muscle cell senescence via stimulation of endoplasmic reticulum stress-induced reactive oxygen species.

Senescence of vascular smooth muscle cells (VSMCs) is a key contributor to plaque vulnerability in atherosclerosis (AS), which is affected by endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the crosstalk between ER stress and ROS production in the pathogenesis of VSMC senescence remains to be elucidated. ER-associated degradation (ERAD) is a complex process that clears unfolded or misfolded proteins to maintain ER homeostasis. HRD1 is the major E3 ligase in mammalian ERAD machineries that catalyzes ubiquitin conjugation to the unfolded or misfolded proteins for degradation. Our results showed that HRD1 protein levels were reduced in human AS plaques and aortic roots from ApoE-/- mice fed with high-fat diet (HFD), along with the increased ER stress response. Exposure to cholesterol in VSMCs activated inflammatory signaling and induced senescence, while reduced HRD1 protein expression. CRISPR Cas9-mediated HRD1 knockout (KO) exacerbated cholesterol- and thapsigargin-induced cell senescence. Inhibiting ER stress with 4-PBA (4-Phenylbutyric acid) partially reversed the ROS production and cell senescence induced by HRD1 deficiency in VSMCs, suggesting that ER stress alone could be sufficient to induce ROS production and senescence in VSMCs. Besides, HRD1 deficiency led to mitochondrial dysfunction, and reducing ROS production from impaired mitochondria partly reversed HRD1 deficiency-induced cell senescence. Finally, we showed that the overexpression of HDR1 reversed cholesterol-induced ER stress, ROS production, and cellular senescence in VSMCs. Our findings indicate that HRD1 protects against senescence by maintaining ER homeostasis and mitochondrial functionality. Thus, targeting HRD1 function may help to mitigate VSMC senescence and prevent vascular aging related diseases. TRIAL REGISTRATION: A real-world study based on the discussion of primary and secondary prevention strategies for coronary heart disease, URL:https://www.clinicaltrials.gov, the trial registration number is [2022]-02-121-01.

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress.

Phenotypic change of vascular smooth muscle cells (VSMCs) is the main contributor of vascular pathological remodeling in atherosclerosis. The endoplasmic reticulum (ER) is critical for maintaining VSMC function through elimination of misfolded proteins that impair VSMC cellular function. ER-associated degradation (ERAD) is an ER-mediated process that controls protein quality by clearing misfolded proteins. One of the critical regulators of ERAD is HRD1, which also plays a vital role in lipid metabolism. However, the function of HRD1 in VSMCs of atherosclerotic vessels remains poorly understood. The level of HRD1 expression was analyzed in aortic tissues of mice fed with a high-fat diet (HFD). The H&E and EVG (VERHOEFF'S VAN GIESON) staining were used to demonstrate pathological vascular changes. IF (immunofluorescence) and WB (western blot) were used to explore the signaling pathways in vivo and in vitro. The wound closure and transwell assays were also used to test the migration rate of VSMCs. CRISPR gene editing and transcriptomic analysis were applied in vitro to explore the cellular mechanism. Our data showed significant reduction of HRD1 in aortic tissues of mice under HFD feeding. VSMC phenotypic change and HRD1 downregulation were detected by cholesterol supplement. Transcriptomic and further analysis of HRD1-KO VSMCs showed that HRD1 deficiency induced the expression of genes related to ER stress response, proliferation and migration, but reduced the contractile-related genes in VSMCs. HRD1 deficiency also exacerbated the proliferation, migration and ROS production of VSMCs induced by cholesterol, which promoted the VSMC dedifferentiation. Our results showed that HRD1 played an essential role in the contractile homeostasis of VSMCs by negatively regulating ER stress response. Thus, HRD1 in VSMCs could serve as a potential therapeutic target in metabolic disorder-induced vascular remodeling.

Clinical treatment of patients with scrub typhus-induced liver injury and intracranial infection.

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi, a bacterium within the family Rickettsiaceae. The clinical symptoms are usually acute and are characterized by fever, eschar formation or ulceration, local or generalized lymphadenopathy, and rash. Because of the extensive damage to small blood vessels throughout the body, scrub typhus can involve multiple systems and organs, causing damage to the respiratory, digestive, and nervous systems and inducing kidney and liver dysfunction. Death can occur in severe cases. We herein report two cases of scrub typhus with liver damage and intracranial infection. Among patients with scrub typhus, the risk of death is significantly higher in those who develop liver injury and intracranial infection. However, there are few reports on the treatment of patients with liver injury and intracranial infection caused by scrub typhus, and relevant treatment experience is thus lacking. Our clinical case report helps to fill the knowledge gap in this area.

Risk factors for progression to bacteremia among patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia in the Intensive Care Unit.

Antibiotic-resistant Acinetobacter baumannii (A. baumannii) is a common cause of hospital-acquired infections. This study aimed to identify independent factors associated with progression from nosocomial pneumonia to bacteremia in patients infected with carbapenem-resistant A. baumannii (CR-AB). From 2019 to 2021, we conducted a retrospective anaylsis of the medical records of 159 nosocomial CR-AB pneumonia patients in our Intensive Care Unit (ICU). We employed both univariate and multivariable logistic regression models to identify factors associated with the progression of nosocomial CR-AB pneumonia to bacteremia. Among the 159 patients with nosocomial CR-AB pneumonia, 40 experienced progression to bacteremia and 38 died within 28 days following diagnosis. Patients who developed bacteremia had a significantly higher 28-day mortality rate compared to those without bloodstream infection (47.50% vs. 15.97%). Multivariable logistic regression revealed that higher levels of C-Reactive protein (CRP) (OR = 1.01) and the use of continuous veno-venous hemofiltration (CVVH) treatment (OR = 2.93) were independently associated with an elevated risk of developing bacteremia. Among patients who developed bloodstream infection, those who died within 28 days exhibited significantly higher level of interleukin-6 (IL-6), a greater frequency of antifungal drugs usage, and a longer duration of machanical ventilation compared to survivors. Furthermore, the use of antifungal drugs was the only factor that associated with 28-day mortality (OR = 4.70). In ICU patients with central venous catheters who have CR-AB pneumonia and are on mechanical ventilation, higher CRP levels and CVVH treatment are risk factors for developing bacteremia. Among patients with bacteremia, the use of antifungal drugs is associated with 28-day mortality.

Exogenous Hydrogen Sulfide Activates PI3K/Akt/eNOS Pathway to Improve Replicative Senescence in Human Umbilical Vein Endothelial Cells.

Background: Endothelial cell senescence is one of the key mechanistic factors in the pathogenesis of atherosclerosis. In terms of molecules, the phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling plays an important role in the prevention and control of endothelial cell senescence, while hydrogen sulfide (H2S) improves the induced precocious senescence of endothelial cells through the PI3K/Akt/eNOS pathway. Comparatively, replicative senescence in endothelial cells is more in line with the actual physiological changes of human aging. This study aims to investigate the mechanism by which H2S improves endothelial cell replicative senescence and the involvement of the PI3K/Akt/eNOS pathway. Methods: we established a model of replicative senescence in human umbilical vein endothelial cells (HUVECs) and explored the effect of 200 µmol/L sodium hydrosulfide (NaHS; a donor of H2S) on senescence, which was determined by cell morphology, the expression level of plasminogen activator inhibitor 1 (PAI-1), and the positive rate of senescence-associated ß-galactosidase (SA-ß-Gal) staining. Cell viability was detected by MTT assay to evaluate the effect of NaHS and the PI3K inhibitor, LY294002. Meanwhile, the protein expression of PI3K, Akt, p-Akt, and eNOS in endothelial cells of each group was detected by Western blot. Results: the replicative senescence model was established in HUVECs at the passage of 16 cumulative cell population doubling values (CPDL). Treatment with NaHS not only significantly reduced the expression of PAI-1 and the positive rate of SA-ß-Gal in HUVEC's replicative senescence model but also notably increased the expression of PI3K, p-Akt, p-eNOS, and the content of nitric oxide(NO). However, the effects of NaHS on the expression of the pathway and the content of NO in HUVECs were abolished when LY294002 specifically inhibited PI3K. Conclusion: NaHS improves the replicative senescence of HUVECs with the contribution of the PI3K/Akt/eNOS pathway.

Therapeutic effect of two methods on avulsion fracture of tibial insertion of anterior cruciate ligament.

BACKGROUND: The tibial stop of anterior cruciate ligament (ACL) is fan-shaped and attached to the medial groove in front of the intercondylar spine, which is located between the anterior horn of the medial and lateral meniscus. The incidence of this fracture is low previously reported, which is common in children and adolescents. With the increase of sports injury and traffic injury and the deepening of under-standing, it is found that the incidence of the disease is high at present. AIM: To explore the difference between open reduction and internal fixation with small incision and high-intensity non-absorbable suture under arthroscopy in the treatment of tibial avulsion fracture of ACL. METHODS: Seventy-six patients with tibial avulsion fracture of anterior cruciate ligament diagnosed and treated in Guanyun County People's Hospital from April 2018 to June 2020 were retrospectively analyzed. According to the surgical methods, they were divided into group A (40 cases) and group B (36 cases). Patients in group A were treated with arthroscopic high-strength non-absorbable suture, and patients in group B were treated with small incision open reduction and internal fixation. The operation time, fracture healing time, knee joint activity and functional score before and after operation, and surgical complications of the two groups were compared. RESULTS: The operation time of group A was higher than that of group B, and the difference was statistically significant (P < 0.05); the fracture healing time of group A was compared with that of group B, and the difference was not statistically significant (P > 0.05); The knee joint function activity was compared between two groups before operation, 3 mo and 6 mo after operation, and the difference was not statistically significant (P > 0.05); the knee joint function activity of group A and group B at 3 mo and 6 mo after operation was significantly higher than that before operation (P < 0.05); the limp, support, lock, instability, swelling, upstairs, squatting, pain and Lysholm score were compared between the two groups before and 6 mo after operation, and the difference was not statistically significant (P > 0.05); the scores of limp, support, lock, instability, swelling, upstairs, squatting, pain and Lysholm in group A and group B at 6 mo after operation were significantly higher than those before operation (P > 0.05); the surgical complication rate of group A was 2.63%, which was lower than 18.42% of group B, and the difference was statistically significant (P > 0.05). CONCLUSION: Both small incision open reduction and internal fixation and arthroscopic high-strength non-absorbable sutures can achieve good results in the treatment of anterior cruciate ligament tibial avulsion fractures. The operation time of arthroscopic high-strength non-absorbable sutures is slightly longer, but the complication rate is lower.

Clinical characteristics of 14 cases of severe Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing: A case series.

INTRODUCTION: The objective of this study was to explore the clinical, laboratory, and imaging features of severe Chlamydia psittaci pneumonia in order to improve early diagnosis and treatment success rates. METHODS: We conducted a retrospective record review of 14 cases of severe Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing technology in our hospital. We extracted and analyzed data on the clinical symptoms and signs, contact history, laboratory investigations, chest computed tomography, treatment, and clinical outcomes. RESULTS: Of the 14 patients, 12 (86%) were male and two (14%) were female, with a mean age of 57 years (SD: 7 years). Eleven patients (79%) had a history of poultry contact. The main clinical manifestations were fever (n = 14, 100%), flu-like symptoms (n = 10, 71%), cough, sputum (n = 9, 64%), and dyspnea (n = 5, 36%). Blood tests revealed marked elevation of neutrophil percentage, C-reactive protein, procalcitonin, brain natriuretic peptide, and creatine kinase levels; slight elevation of aspartate aminotransferase, creatinine, urea, fibrinogen, and D-dimer levels; and decreased albumin, sodium, and calcium levels. Chest computed tomography showed bilateral lesions (n = 7, 50%), middle-lower lobe lesions (n = 10, 71%), lesions in multiple lobes (n = 9, 64%), consolidation shadows (n = 11, 79%), and pleural effusions (n = 11, 79%). The median time from disease onset to hospital admission was 4.5 days (interquartile range: 1-17 days); the mean length of hospital stay was 20.9 ±â€Š8.5 days, and the mean time from admission to diagnosis was 5.1 ±â€Š2.6 days. After diagnosis, patients were either treated with doxycycline alone or doxycycline combined with quinolones. All 14 patients developed respiratory failure and received invasive mechanical ventilation; two (14%) received veno-venous extracorporeal membrane oxygenation, four (29%) received continuous renal replacement therapy, and three (21%) died. DISCUSSION AND CONCLUSION: A poultry contact history and typical flu-like symptoms are early indicators of Chlamydia psittaci pneumonia. Substantial elevations in procalcitonin, creatine kinase, and brain natriuretic peptide indicate severe disease. Metagenomic next-generation sequencing is useful for diagnosis. Early empirical antibiotic therapy with quinolones can reduce the mortality in critically ill patients.

Severe Chlamydia psittaci Pneumonia Complicated by Rhabdomyolysis: A Case Series.

Purpose: To explore the clinical characteristics, diagnosis, and treatment of severe Chlamydia psittaci pneumonia complicated by rhabdomyolysis and to improve the success rate of treatment. Patients and Methods: The clinical characteristics, diagnosis, treatment, and outcomes of four patients with severe C. psittaci pneumonia complicated by rhabdomyolysis diagnosed by metagenomic next-generation sequencing (mNGS) in our hospital were analyzed retrospectively. Results: All four patients were male, aged 46-64 years, and all had a history of bird contact. All patients had fever, fatigue, tea-colored urine, myalgia, and two patients were unable to walk. C. psittaci DNA was found by mNGS of the bronchoalveolar lavage fluid of all four patients. Their creatine kinase was >1000 U/L, and myoglobin, C-reactive protein, procalcitonin, and brain natriuretic peptide were significantly increased. The McMahon score of three patients was >6 points, of whom one patient suffered from acute kidney injury; he was treated with continuous renal replacement therapy and eventually died. After diagnosis, three patients were treated with doxycycline and quinolones and were discharged after recovery. Conclusion: Psittacosis complicated by rhabdomyolysis is characterized by fever, fatigue, myalgia, and tea-colored urine, with significant increases in creatine kinase and myoglobin. The McMahon score should be applied early to assess the risk of acute kidney injury, and renal replacement therapy and renal protection therapy should be initiated in the early stage. Among severely ill patients, early use of empirical antibiotics, including quinolones, may improve the prognosis.