Incidence and Impact of Takotsubo Syndrome in Hospitalized Patients With COVID-19.

BACKGROUND: Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients hospitalized with COVID-19. METHODS: A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities. RESULTS: A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non-takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs $78,468) (all P < .001). After matching and compared with the non-takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs $79,523; P < .001). CONCLUSION: Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19.

Pore structure characterization and its influence on aqueous phase trapping damage in tight gas sandstone reservoirs.

Aqueous phase trapping (APT), which is one of the most prominent damages, seriously restricts the natural gas production in tight gas sandstone with low permeability. Pore size and microscopic pore structures are the most important factors to determine the water blocking damage. In this paper, 9 core samples from tight gas sandstone with various physical properties were employed, and the pore size distribution (PSD) of the core samples were investigated by high pressure mercury intrusion tests (HPMI). Results showed that the porosity of core samples ranges from 5.68% to 13.7%, and the permeability ranges from 0.00456 to 7.86 mD, which is a typical tight reservoir with strong heterogeneity. According to the HPMI capillary curve, the cores can be divided into two types: Type I and Type II, and the pore sizes of type I are larger than that of type II. Fractal distributions were obtained using HPMI data to further determine the pore structure characteristics of tight reservoirs. The pore structures of tight sandstones display the multifractal fractal feature: D1 corresponding to macro-pores, and D2 corresponding to fractal dimension of micro-pores. Furthermore, APT damage was determined by the permeability recovery ratios (Kr) after gas flooding tests. The correlation of Kr and PSD and fractal dimensions were jointly analyzed in tight gas sandstone. Although positive correlations between pore size parameters and the permeability recovery ratios were observed with relatively weak correlations, for those core samples with very close permeability, pore size parameters (both permeability and PSD) is inadequate in clarifying this damage. The fractal dimension can well describe the complexity and heterogeneity of flow channels in pores, which can become the determining factor to distinguish the flow capacity of tight sandstone. The D2 for samples of type I and type II exhibited a good negative relation with Kr with a correlation coefficient of 0.9878 and 0.7723, respectively. The significance of this finding is that for tight gas sandstone, fractal dimensions, especially the small pore fractal dimension (D2), can be used to predict the possible APT damage very well.

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.

Takotsubo syndrome and vaccines: a systematic review.

AIMS: Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by vaccination. METHODS AND RESULTS: We did a systematic review, searching PubMed, Embase, Web of Science, Ovid MEDLINE, Journals@Ovid, and Scopus databases up to 26 April 2023 to identify case reports or case series of vaccine-induced TTS. We then extracted and summarized the data from these reports. Eighteen reports were identified, with a total of 19 patients with TTS associated with vaccinations. Of the 19 included patients, the majority were female (n = 13, 68.4%) with a mean age of 56.6 ± 21.9 years. Seventeen patients developed TTS after coronavirus disease 2019 vaccination, 14 of whom received an mRNA vaccination. Two cases of TTS occurred after influenza vaccination. Among the 19 patients, 17 (89.5%) completed transthoracic echocardiography and 16 (84.2%) underwent angiography procedures. Seven patients (36.8%) completed cardiac magnetic resonance imaging. The median time to symptom onset was 2 (inter-quartile range, 1-4) days. The most common symptoms were chest pain (68.4%), dyspnoea (57.9%), and digestive symptoms (31.6%). A total of 57.9% of patients developed nonspecific symptoms such as fatigue, myalgia, diaphoresis, and fever. Among the 16 reported cases of TTS, 15 patients (93.8%) exhibited elevated cardiac troponin levels, while among the nine reported cases, eight patients (88.9%) had elevated natriuretic peptide levels. All patients had electrocardiographic changes: ST-segment change (47.1%), T-wave inversion (58.8%), and prolonged corrected QT interval (35.3%). The most common TTS type was apical ballooning (88.2%). Treatment during hospitalization typically included beta-blockers (44.4%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (33.3%), and diuretics (22.2%). After treatment, 81.3% of patients were discharged with improved symptoms. Among this group, nine patients (56.3%) were reported to have recovered ventricular wall motion during follow-up. Two patients (12.5%) died following vaccination without resuscitation attempts. CONCLUSIONS: TTS is a rare but potentially life-threatening complication of vaccination. Typical TTS symptoms such as chest pain and dyspnoea should be considered alarming symptoms, though nonspecific symptoms are common. The risks of such rare adverse events should be balanced against the risks of infection.

Incidence and Impact of Acute Pericarditis in Hospitalized Patients With COVID-19.

Background Acute pericarditis (AP) is considered a cardiovascular complication in patients with COVID-19. We aimed to ass-ess the incidence, associated complications, and clinical impact of AP on hospitalized patients with COVID-19. Methods and Results In this retrospective cohort study, International Classification of Diseases, Tenthth Revision, Clinical Modification (ICD-10) codes were used to identify patients with COVID-19 with or without AP in the National Inpatient Sample 2020 database. We compared outcomes between AP and non-AP groups before and after propensity-score matching for patient and hospital demographics and relevant comorbidities. A total of 211 619 patients with a primary diagnosis of COVID-19 were identified, including 983 (0.46%) patients who had a secondary diagnosis of AP. Before matching, patients with COVID-19 with AP were younger (59.93±19.24 years old versus 64.29±16.82 years old) and more likely to have anemia (40.5% versus 19.9%), cancer (6.7% versus 3.6%), and chronic kidney disease (29.3% versus 19.6%) (all P<0.05). After matching, patients with COVID-19 with AP (n=980), when compared with the matched non-AP group (n=2936), had higher rates of mortality (21.3% versus 11.1%, P<0.001), cardiac arrest (5.0% versus 2.6%, P<0.001), cardiogenic shock (4.2% versus 0.5%, P<0.001), ventricular arrhythmia (4.7% versus 1.9%, P<0.001), acute kidney injury (38.3% versus 28.9%, P<0.001), acute congestive heart failure (14.3% versus 4.8%, P<0.001), and longer length of stay (7.00±10.00 days versus 5.00±7.00 days, P<0.001) and higher total charges ($75066.5±$130831.3 versus $44824.0±$63660.5, P<0.001). Conclusions In hospitalized patients with COVID-19, AP is a rare but severe in-hospital complication and is associated with worse in-hospital outcomes.

The association of coagulation indicators with in-hospital acute kidney injury and malignant events of patients with acute aortic dissection: a retrospective cohort study.

Background: Acute kidney injury (AKI) is a prevalent complication of acute aortic dissection (AAD) and is associated with poor outcomes. The onset of AAD may result in endothelial injury due to the formation of the false lumen, which can activate the coagulation pathway and lead to coagulation dysfunction. It serves as a valuable diagnostic and prognostic marker for AAD, but also plays a role in the pathological mechanisms underlying AKI. We aimed to investigate the potential value of coagulation indicators at admission for assessing in-hospital AKI and malignant events after AAD. Methods: We identified patients with AAD admitted to the First Affiliated Hospital of Shantou University Medical College from January 2015 to October 2020 and divided them into two groups according to coagulation function. Univariable and multivariable analyses were used to analyze the association between coagulation indicators and AKI and malignant events in patients with AAD. Chi-squared or Fisher exact test and receiver operating characteristic (ROC) curve analysis was conducted to assess the value of coagulation indicators in predicting in-hospital AKI and malignant events. Results: A total of 487 patients were enrolled in this study, including 309 cases with normal coagulation. After the multivariable adjustment, the incidence of in-hospital AKI in the abnormal coagulation group was significantly higher [model 1: 2.061 (1.214-3.501), P=0.007; model 2: 1.833 (1.058-3.177), P=0.031; model 3: 1.836 (1.048-3.216), P=0.034]. The incidence of malignant events was higher in the abnormal prothrombin time (PT) group [model 1: 4.283 (0.983-18.665), P=0.053; model 2: 7.342 (1.467-36.749), P=0.015; model 3: 6.996 (1.377-35.537), P=0.019]. Chi-squared and Fisher exact test showed that PT and abnormal coagulation score (ACS) were statistically different among the AKI groups and malignant event groups. Under ROC analysis, coagulation indicators were helpful to predict AKI (AUC =0.668; P<0.001). Conclusions: Our study confirmed the presence of coagulation dysfunction is associated with an increased risk of AKI and malignant events. It suggested the severity of coagulation dysfunction is positively correlated with the incidence of in-hospital AKI in AAD patients. These results highlight the importance of considering coagulation dysfunction as a potential mechanism underlying AKI and malignant events after AAD.

Microglia-dependent excessive synaptic pruning leads to cortical underconnectivity and behavioral abnormality following chronic social defeat stress in mice.

Synapse loss in medial prefrontal cortex (mPFC) has been implicated in stress-related mood disorders, such as depression. However, the exact effect of synapse elimination in the depression and how it is triggered are largely unknown. Through repeated longitudinal imaging of mPFC in the living brain, we found both presynaptic and postsynaptic components were declined, together with the impairment of synapse remodeling and cross-synaptic signal transmission in the mPFC during chronic stress. Meanwhile, chronic stress also induced excessive microglia phagocytosis, leading to engulfment of excitatory synapses. Further investigation revealed that the elevated complement C3 during the stress acted as the tag of synapses to be eliminated by microglia. Besides, chronic stress induced a reduction of the connectivity between the mPFC and neighbor regions. C3 knockout mice displayed significant reduction of synaptic pruning and alleviation of disrupted functional connectivity in mPFC, resulting in more resilience to chronic stress. These results indicate that complement-mediated excessive microglia phagocytosis in adulthood induces synaptic dysfunction and cortical hypo-connectivity, leading to stress-related behavioral abnormality.

Impact of malnutrition on in-hospital outcomes in takotsubo cardiomyopathy.

OBJECTIVE: This study assesses the effect of malnutrition on the in-hospital outcomes of patients with takotsubo cardiomyopathy (TCM). METHODS: We performed a retrospective cohort analysis using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for a primary diagnosis of TCM from the National Inpatient Sample database (2016-2018). A concurrent diagnosis of malnutrition was then identified, and these patients were divided into the malnutrition group and non-malnutrition group. To adjust for underlying risk factors, a multivariable logistic regression model was employed followed by a propensity score matching analysis for the malnutrition and the non-malnutrition group. We then compared the in-hospital outcomes between these two groups. RESULTS: Among 4733 patients with a primary diagnosis of TCM, 221 (4.7%) patients with TCM were found to be malnourished. After propensity score matching, patients with TCM with malnutrition were found to have a higher mortality rate (8.3% versus 2.0%, P < 0.001), a higher rate of complications including cardiogenic shock (16.1% versus 7.0%, P < 0.001), ventricular arrhythmia (8.8% versus 3.9%, P = 0.01), acute kidney injury (24.9% versus 10.6%, P < 0.001), and acute respiratory failure (32.7% versus 17.8%, P < 0.001). There was no statistically significant difference in the incidence of cardiac arrest between the two groups. Malnutrition of severe degree was associated with a sevenfold (odds ratio 6.8, 95% confidence interval, 3.2-13.4) increased risk of in-hospital mortality compared with those without malnutrition. CONCLUSION: Patients with malnutrition who were admitted with TCM were associated with higher rates of in-hospital mortality and complications compared with those without malnutrition.

Reductive Catalytic Depolymerization of Semi-industrial Wood-Based Lignin.

The current work studies the reductive catalytic depolymerization (RCD) of lignin from a novel semi-industrial process. The aim was to obtain aromatic mono-, di-, tri-, and tetramers for further valorization. The substrate and products were characterized by multiple analytical methods, including high pressure size-exclusion chromatography (HPSEC), gas chromatography-mass spectrometry, GC-flame ionization detector (FID), GC-FID/thermal conductivity detector (TCD), and NMR. The RCD was studied by exploring the influence of different parameters, such as lignin solubility, reaction time, hydrogen pressure, reaction temperature, pH, type and loading of the catalyst, as well as type and composition of the organic/aqueous solvent. The results show that an elevated temperature, a redox catalyst, and a hydrogen atmosphere are essential for the depolymerization and stability of the products, while the reaction medium also plays an important role. The highest obtained mono- to tetramers yield was 98% and mono- to dimers yield over 85% in the liquid phase products. The reaction mechanisms influenced the structure of the aliphatic chain in the monomers, but left the phenolic structure along with the methoxy groups largely unaltered. The current work contributes to the development and debottlenecking of the novel and sustainable overall process, which utilizes efficiently all the fractions of wood, in line with the principles of green engineering and chemistry.

Prognostic factors of Takotsubo cardiomyopathy: a systematic review.

Takotsubo cardiomyopathy (TCM), characterized by reversible ventricular dysfunction, has similar mortality to acute coronary syndrome. With the growing interest in the diagnosis of and interventions for TCM, many risk factors had been found to affect the prognosis of TCM patients, such as age, sex, and pre-existing diseases. Because of the incomplete understanding of the pathophysiologic mechanism in TCM, evidence-based medical therapy for this condition is lacking. Early intervention on risk factors may improve the outcomes of TCM. In this review, we sought to provide up-to-date evidence on risk factors and medical therapies that affect TCM outcome. We found that male sex, physical triggers, and certain comorbidities such as chronic kidney disease, malignant disease, higher body mass index, sepsis, chronic obstructive pulmonary disease, and anaemia were associated with poor TCM prognosis. In contrast, race, hyperlipidaemia, diabetes mellitus, and mood disorders were not clearly associated with TCM prognosis. We also reviewed the effect of medical therapies on TCM outcome, including angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, calcium channel blockers, and statins. The evidence that these medications confer a survival benefit on TCM patients is limited. Understanding these prognostic factors could help develop risk-stratification tools for TCM and establish effective prevention and interventions for this not-so-benign condition. Further multicentre clinical studies with large samples and meta-analyses of findings from previous studies are needed to address the inconsistent findings among the many potential risk factors for TCM.

Conventional cardiovascular risk factors associated with Takotsubo cardiomyopathy: A comprehensive review.

Takotsubo cardiomyopathy (TCM), characterized by transient left ventricular dysfunction, was first reported in Japan in 1990. Current research suggests that TCM can be affected by conventional cardiovascular factors such as hypertension (HTN), diabetes, hyperlipidemia (HLD), and obesity. Despite the increasing interest in this disease, research on TCM remains limited. Conventional cardiovascular factors are clinically related to the outcome of TCM. We reviewed the publications published in PubMed database between January 01 2010 and January 15 2021, and summarized the most current available evidence on the correlation between TCM and the conventional cardiovascular factors. TCM patients are predominantly postmenopausal women. Men and young patients are less commonly seen, but are prone to acute adverse complications and poor prognosis. HTN is common in patients with recurrent TCM. Existing evidence suggests that obesity and chronic kidney disease are related to poor prognosis in TCM. HLD is reported to be associated with fewer complications, though current evidence is limited. Finally, the relationship between diabetes and TCM prognosis is ambivalent. Current evidence suggests conventional cardiovascular risk factors are associated with the outcome of TCM, especially with mortality and complications. More prospective studies are needed to clarify the relationship between each risk factor and the prognosis of TCM.

Anemia Is Associated With Poor Clinical Outcomes in Hospitalized Patients With Takotsubo Cardiomyopathy.

The association between anemia and Takotsubo cardiomyopathy (TCM) has not been well studied. To assess the effect of anemia on patients hospitalized with TCM, we identified 4733 patients with a primary diagnosis of TCM from the 2016 to 2018 National Inpatient Sample (NIS) database (the United States) using the International Classification of Diseases, 10th edition, Clinical Modification (ICD-10-CM) code. Of these, 603 (12.7%) patients had a comorbidity of anemia and 4130 did not. After propensity score matching, we compared the in-hospital outcomes between the 2 groups (anemia vs nonanemia, n = 594 vs 1137). Patients with TCM with anemia had significantly higher rates of in-hospital complications, including cardiogenic shock (11.4% vs 4.0%, P < .001), ventricular arrhythmia (6.6% vs 3.6%, P = .008), acute kidney injury (22.7% vs 13.1%, P < .001), acute respiratory failure (22.6% vs 13.1%, P < .001), longer length of hospital stay (5.6 ± 5.8 days vs 3.6 ± 3.6 days, P < .001), and higher total charges (US$79 586 ± 10 2436 vs US$50 711 ± 42 639, P < .001). In conclusion, patients with anemia who were admitted for TCM were associated with a higher incidence of in-hospital complications compared with those without anemia.

The Association Between Hyperlipidemia and In-Hospital Outcomes in Takotsubo Cardiomyopathy.

PURPOSE: Hyperlipidemia (HLD) is one of the most common cardiovascular risk factors and is prevalent in patients with takotsubo cardiomyopathy (TCM), but the association between HLD and TCM patients' outcomes is unclear. We investigated the impact of HLD on the in-hospital outcomes of TCM patients. PATIENTS AND METHODS: Our retrospective cohort study used the latest available data from the National Inpatient Sample (2016-2017). Using the ICD-10 code, we identified 3139 patients with a primary diagnosis of TCM, 1530 of whom had HLD. We compared in-hospital outcomes between HLD and non-HLD groups before and after propensity score matching. RESULTS: In the unmatched cohort, the HLD group had lower incidences of cardiac arrest, cardiogenic shock, and acute respiratory failure (ARF); shorter length of stay (LOS); and lower total charges (All p<0.05). In-hospital mortality (p=0.102) and ventricular arrhythmia (p=0.235) rates did not differ. After propensity score matching, the HLD group had lower rates of in-hospital mortality (1.1% vs 2.4%, p=0.027), ARF (9.1% vs 12.1%, p = 0.022) and cardiogenic shock (3.4% vs 5.6%, p=0.012), shorter LOS (3.20 ± 3.27 days vs 3.57 ± 3.14 days, p=0.005), and lower total charges (p=0.013). The matched groups did not differ significantly regarding cardiac arrest (p=0.141), ventricular arrhythmia (p=0.662) or acute kidney injury (AKI) (p = 0.167). CONCLUSION: Counterintuitively, HLD was associated with better in-hospital outcomes in both the unmatched and propensity-matched cohorts of hospitalized TCM patients. Further studies are needed to investigate the mechanisms that may contribute to the association in TCM patients with HLD.

The Impact of COPD on in-Hospital Outcomes in Patients with Takotsubo Cardiomyopathy.

Purpose: Chronic obstructive pulmonary disease (COPD) is a known comorbidity of takotsubo cardiomyopathy (TCM), and COPD exacerbation is a potential triggering factor of TCM. The association between COPD and in-hospital outcomes and complications among TCM patients is not well established. We sought to assess the effect of COPD on hospitalized patients with a primary diagnosis of TCM. Methods: We conducted a retrospective cohort study in patients with a primary diagnosis of TCM with or without COPD using the latest National Inpatient Sample from 2016-2017. We identified 3139 patients admitted with a primary diagnosis of TCM by the ICD-10-CM coding system; 684 of those patients also had a diagnosis of COPD. We performed propensity score matching in a 1:2 ratio (n=678 patients, matched COPD group; n=1070, matched non-COPD group) and compared in-hospital outcomes and complications between TCM patients with and without a COPD diagnosis. Results: Before matching, the COPD group had worse outcomes compared with the non-COPD group in inpatient death (2.9% vs 1.3%, p=0.006), length of stay (LOS) (4.02±2.99 days vs 3.27±3.39 days, p<0.001), hospitalization charges ($55,242.68±47,637.40 vs $48,316.97±47,939.84, p=0.001), and acute respiratory failure (ARF) (22.5% vs 7.7%, p<0.001), respectively. After propensity score matching, the matched COPD group, compared with the matched non-COPD group, had a higher inpatient mortality rate (2.9% vs1.0%, p=0.005), longer LOS (4.02±3.00 days vs 3.40±3.54 days, p<0.001), higher hospitalization charges ($55,409.23±47,809.13 vs $46,469.60±42,209.10, p<0.001), and a higher incidence of ARF (22.6% vs 8.2%, p<0.001) and cardiogenic shock (5.6% vs 3.3%, p=0.024), respectively. Conclusion: Patients with COPD who are hospitalized for TCM have higher rates of inpatient mortality, ARF, cardiogenic shock, as well as a longer LOS, and higher charges of stay than those without COPD. Prospective studies are warranted to examine the effect of early intervention or treatment of COPD on short- and long-term outcomes of TCM.

Hippocampal CD39/ENTPD1 promotes mouse depression-like behavior through hydrolyzing extracellular ATP.

Emerging evidence implicates that low levels of ATP in the extracellular space may contribute to the pathophysiology of major depressive disorder (MDD). The concentration of extracellular ATP is regulated by its hydrolase ectonucleotide tri(di)phosphohydrolase (ENTPD). However, the role of ENTPD in depression remains poorly understood. Here we examine the role of CD39 (known as ENTPD1) in mouse depression-like behavior induced by chronic social defeat stress (CSDS). We demonstrate that CSDS enhances the expression and activity of CD39 in hippocampus. The CD39 functional analog apyrase also induces depression-like behavior, which can be ameliorated by ATP replenishment. Pharmacological inhibition and genetic silencing of CD39 has an antidepressant-like effect via increasing hippocampal extracellular ATP concentration, accompanied with an increase in hippocampal neurogenesis and dendritic spine numbers in defeated mice. These results suggest that hippocampal CD39 contributes to CSDS-induced depression-like behavior via hydrolyzing extracellular ATP, indicating that CD39 may be a promising new target for the treatment of depression.

The association between anxiety disorders and in-hospital outcomes in patients with myocardial infarction.

BACKGROUND: Anxiety disorders are prevalent in patients with myocardial infarction (MI), but the effects of anxiety disorders on in-hospital outcomes within MI patients have not been well studied. HYPOTHESIS: To examine the effects of concurrent anxiety disorders on in-hospital outcomes in MI patients. METHODS: We conducted a retrospective cohort study in patients with a principal diagnosis of MI with and without anxiety disorders in the National Inpatient Sample 2016. A total of 129 305 primary hospitalizations for acute MI, 35 237 with ST-segment elevation myocardial infarction (STEMI), and 94 068 with non-ST elevation myocardial infarction (NSTEMI) were identified. Of these, 13 112 (10.1%) had anxiety (7.9% in STEMI and 11.0% in NSTEMI). We compared outcomes of anxiety and nonanxiety groups after propensity score matching for the patient and hospital demographics and relevant comorbidities. RESULTS: After propensity score matching, the anxiety group had a lower incidence of in-hospital mortality (3.0% vs 4.4%, P < .001), cardiac arrest (2.1% vs 2.8%, P < .001), cardiogenic shock (4.9% vs 5.6%, P = .007), and ventricular arrhythmia (6.7% vs 7.9%, P < .001) than the nonanxiety group. In the NSTEMI subgroup, the anxiety group had significantly lower rates of in-hospital mortality (2.3% vs 3.5%, P < .001), cardiac arrest (1.1% vs 1.5%, P = .008), and cardiogenic shock (2.8% vs 3.5%, P = .008). In the STEMI subgroup, we found no differences in in-hospital outcomes (all P > .05) between the matched groups. CONCLUSION: Although we found that anxiety was associated with better in-hospital outcomes, subgroup analysis revealed that this only applied to patients admitted for NSTEMI instead of STEMI.

Pannexin-1 channel dysfunction in the medial prefrontal cortex mediates depressive-like behaviors induced by chronic social defeat stress and administration of mefloquine in mice.

Mefloquine (MFQ) is widely used for the treatment of malaria clinically. Apart from antimalarial effect, psychiatric side effects such as depression and anxiety of MFQ have been reported. Interestingly, MFQ is also known as a broad-spectrum pannexin-1 (Panx1) inhibitor. Panx1 is a new gap junction channel in the brain which mediates efflux of adenosine triphosphate (ATP). Although exogenous ATP has been known to produce a potential antidepressant-like effect, little is known about the role of Panx1 in pathophysiology of depression, especially the depression induced by administration of MFQ. Here, we used the chronic social defeat stress (CSDS) model and found a decrease in the expression and function of Panx1 in the medial prefrontal cortex (mPFC) of susceptible mice. Furthermore, pharmacological blockade of Panx1 in the mPFC with carbenoxolone (CBX) (100 mM) or 10Panx (100 µM) was sufficient to induce depressive-like behaviors and increase vulnerability to stress in mice, which were prevented by preconditioning with ATP (25 µM). Finally, systemic and intral-mPFC injection of MFQ both inhibited the activity of Panx1 and induced depressive-like and anxiety behaviors in mice with sub-threshold social defeat stress. Indeed, the behavioral abnormalities induced by MFQ were prevented by preconditioning with ATP in the mPFC. In conclusion, our study demonstrates a role of the Panx1 channel in chronic stress and MFQ-induced depressive-like and anxiety behaviors, which may provide a novel molecular mechanism for psychiatric side effects of MFQ.