Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study.

BACKGROUND: Antiplatelet and anticoagulation drugs complicate acute gastrointestinal bleeding (GIB) patients. Limited data about the risk factors and patient management has been presented. This study explored the association between previous antiplatelet or anticoagulant drug usage and clinical outcomes in GIB patients to improve awareness further and optimize treatment. METHODS: We conducted a multicenter, non-interventional, real-world prospective study in 106 hospitals in 23 provinces in China. GIB patients confirmed in the emergency department were included and were grouped according to previous drug histories. Univariate analysis, multivariate logistic regression, and multivariate stratification models were performed separately to investigate the associations. RESULTS: A total of 2299 patients (57.23 ± 17.21 years old, 68.3% male) were included, of whom 20.1% and 2.9% received antiplatelet and anticoagulation therapy, respectively. The all-cause 28-day mortality rates in patients without antiplatelet or anticoagulants, patients undergoing antiplatelet treatment, and patients with anticoagulation therapy were 2.8%, 4.6%, and 10.5%, respectively. After adjusting for confounding factors, both antiplatelet [odd ratio (OR), 2.92; 95% confidence interval (CI), 1.48-5.76; p = 0.002] and anticoagulation therapy (OR, 8.87; 95% CI, 3.02-26.02; p < 0.001) were associated with higher 28-day mortality. In the subgroup analysis, blood transfusion, especially red blood cell transfusion, in patients undergoing antiplatelet and anticoagulation therapy was associated with a decreased death risk. CONCLUSION: We confirmed an association between concurrent antiplatelet or anticoagulation therapy in GIB patients and elevated 28-day mortality. Blood transfusions could improve poor outcomes in such patients.

Early percutaneous catheter drainage in protecting against prolonged fever among patients with pyogenic liver abscess: a retrospective cohort study.

BACKGROUND: Percutaneous catheter drainage (PCD) has been viewed as first-line treatment for pyogenic liver abscess (PLA), yet detailed guidance is lacking for best practice of PCD. This study investigated characteristics of patients with PLA who had received PCD, identified factors associated with prolonged fever, and aimed to evaluate the relationship between timing of PCD and clinical improvement. METHODS: This was a retrospective study of patients with PLA who had undergone PCD over a 7-year period. PCD performed when the liquefaction degree of abscesses was less than 30% and/or within 1 week after fever onset was defined as early PCD. Patients were grouped and analysed based on the timing of PCD (early vs. delayed). Factors associated with prolonged fever were also analysed using univariate and multivariate logistic regression. RESULTS: Among 231 patients with PLA, 81 treated with PCD were included in the study after exclusion. The size of abscesses ranged from 3.4 to 16 cm in diameter. Interestingly, the abscesses were predominantly multiloculated in this cohort (82.7%). The most common pathogen isolated from pus was Klebsiella pneumoniae (60.5%), followed by Escherichia coli (8.6%). The duration of fever was significantly shortened with early PCD as compared to delayed PCD intervention (p = .042). No statistical differences were found between the two groups with regard to catheter adjustment and salvage drainage. Maximum body temperature and diameter of abscess > 7.5 cm were found to be associated with prolonged fever while early PCD was inversely related to prolonged fever. Multivariate analysis suggested that early PCD treatment was an independent protective factor of prolonged fever (p = .030). CONCLUSIONS: Large abscesses with loculation could be successfully treated with PCD, and early PCD protected patients with PLA from prolonged fever. Our findings suggest that early intervention should be provided if PCD is indicated in clinical practice.KEY MESSAGESLarge abscesses and multiloculated abscesses can be treated with percutaneous catheter drainage.Early percutaneous catheter drainage is identified as a protective factor of prolonged fever among patients with pyogenic liver abscesses.Early intervention should be provided if percutaneous catheter drainage is indicated for pyogenic liver abscesses.

Systemic Lupus Erythematosus and Hereditary Coproporphyria: Two Different Entities Diagnosed by WES in the Same Patient.

Background: Hereditary coproporphyria (HCP) is a rare autosomal dominant disorder caused by a partial deficiency of coproporphyrinogen III oxidase (CPOX), and systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic predisposition. SLC7A7 (solute carrier family 7 member 7) may be associated with monogenic lupus disease; however, only 2 cases of concomitant HCP and SLE have been reported. Methods: We report a 30-year-old woman with a six-year history of SLE presenting with abdominal pain, vomiting, dysuria, tachycardia, and hyponatremia. Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of her pedigree to detect the genetic background. The Gene Expression Omnibus (GEO) database was used to search the related gene expression profiles. Differentially expressed genes (DEGs) were identified using GEO2R. Result: A novel heterozygous splicing mutation of CPOX (NM_000097): c.700+2 T > C (intron 2) was detected by WES in the proband, and it was considered likely pathogenic (PSV1+PM2). Sanger sequencing verified the heterozygous mutation of CPOX in the proband, although it was not detected in her father. WES also identified 62 other gene variants, especially two heterozygous variants in SLC7A7 (NM_001126106): c.250G > A (p. V84I) and c.625+1G > A (splicing). DEGs were detected from GSE51997, and the expression of CPOX was downregulated in SLE patients compared with normal controls (adj. P = 0.0071, logFC = -1.0975). Conclusion: This study presents the first reported case of SLE coexisting with HCP in China; moreover, a novel splicing mutation of CPOX, i.e., c.700+2 T > C (intron 2), and two heterozygous mutations of SLC7A7 were reported. The simultaneous mutations of CPOX and SLC7A7 may explain the etiopathogenetic connections of HCP and SLE.

Prognostic factors and clinical efficacy of second-line treatments of Pneumocystis jirovecii pneumonia for non-HIV patients after first-line treatment failure.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection. In non-HIV immunocompromised patients with PCP, a standard second-line treatment has not been established up to now. METHODS: Non-HIV immunocompromised patients with confirmed PCP between April 2013 and December 2020 were included. Their PCP treatment history was tracked. Factors related to first-line trimethoprim/sulfamethoxazole (TMP/SMX) and second-line treatment failure were identified. Different second-line treatment strategies were compared. RESULTS: Among the 220 patients, 127 (57.73%) did not respond to first-line TMP/SMX treatment. Risk factors related to treatment failure included symptom triad with breathlessness at rest, persistent fever and cough (85% in the treatment failure group versus 74% in the treatment success group, P = 0.034), treatment with invasive mechanical ventilation (67 vs. 19%, P < 0.001), coinfection with CMV (69 vs. 47%, P = 0.035), and bacteremia (59 vs. 10%, P < 0.001). A total of 49 patients received second-line treatment on the basis of TMP/SMX, and 28 (57.1%) of them responded to the treatment. No clinical parameter, including selection of different therapies, was found to be significantly associated with second-line treatment failure. Further, the prognosis of different second-line therapies showed no drug or drug combination strategy superior to others. The primaquine group had lower 90-day mortality rate (45.9%) but showed no statistically significant difference compared with the non-primaquine group (64.6%). The patients in the clindamycin plus primaquine group had the lowest in-hospital mortality rate (22.2%, P = 0.042) among different second-line therapies, although the in-hospital mortality of the primaquine group was not significantly different from that of the non-primaquine group. The differences in 28 day mortality and overall mortality rates were not statistically significant, too. CONCLUSION: CMV infection and bacteremia were risk factors significantly associated with treatment failure of TMP/SMX. The response and survival rates of second-line treatment, including clindamycin, primaquine, and caspofungin, were poor, maybe clindamycin plus primaquine as second line treatment was better than other treatment strategies. These results suggest that clinicians should carefully evaluate whether the treatment of TMP/SMX has failed due to a coinfection rather than hastily changing to a second-line drug when the patient worsens.

In vitro investigation of HBV clinical isolates from Chinese patients reveals that genotype C isolates possess higher infectivity than genotype B isolates.

Hepatitis B virus (HBV) genotype B and C are two major genotypes that are prevalent in Asia and differ in natural history and disease progression. The impact of HBV genotypes on viral replication and protein expression has been explored by the transfection of hepatoma cells with replication-competent HBV DNA, which mimics the later stages of the viral life cycle. However, the influence of HBV genotypes on the early events of viral infection remains undetermined, mainly due to the difficulties in obtaining sufficient infectious viral particles for infection assays. Here, we report that a high-titer HBV inoculum can be generated from the transient transfection-based cell model after optimizing transfection conditions and modifying the HBV-expressing construct. By performing in vitro infection assays using transiently transfected derived viruses, we found that clinical genotype C isolates possessed higher infectivity than genotype B isolates. Moreover, we identified a naturally occurring mutation sL21S in small hepatitis B surface protein, which markedly decreased the infectivity of HBV genotype C isolates, but not that of genotype B isolates. In summary, using infectious viral particles provided by the optimized transient transfection-based cell model, we have been able to investigate a wide range of HBV variants on viral infectivity, which may contribute to our understanding of the reasons for different clinical outcomes in HBV infections and the development of therapeutic drugs targeting the early stages of HBV life cycle.

Klebsiella pneumoniae pneumonia in patients with rheumatic autoimmune diseases: clinical characteristics, antimicrobial resistance and factors associated with extended-spectrum ß-lactamase production.

BACKGROUND: Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum ß-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department. METHODS: We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected. RESULTS: Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing. CONCLUSIONS: K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.

[Role of dendritic cells in lipopolysaccharide induced cardiac dysfunction in mice].

OBJECTIVE: To observe the role of dendritic cells (DC) in lipopolysaccharide (LPS)-induced myocardial dysfunction in mice. METHODS: Eighty wild type male C57BL/6 mice were divided into four groups, according to random number table method: sham group, DC inhibitors in control group (VAG539-sham group), LPS sepsis model group (LPS group) and DC inhibitors pretreatment group (VAG539-LPS group), 20 in each group. The cardiac dysfunction model of sepsis mice was established by LPS intraperitoneal injection; the sham group was injected with the same dose of normal saline. VAG539-sham group and VAG539-LPS group were injected with the DC inhibitor VAG539 (30 mg/kg, twice per day, for 2 days) before injection with normal saline or LPS, respectively. Ten mice in each group were used to observe the 14-day survival rate. Mean arterial pressure (MAP) of the remaining 10 mice was measured through the small animal tail artery cannula; the cardiac function [including the heart rate (HR), left ventricular ejection fraction (LVEF) and short axial shortening rate (FS)] were evaluated by small animal echocardiography; the aggregation and maturation of myocardial DC were detected by flow cytometry; and serum inflammatory factors [including tumor necrosis factor-α (TNF-α), interleukins (IL-12, IL-6)] were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with sham group, the 14-day cumulative survival rate in LPS group was significantly reduced, while HR, MAP, LVEF and FS were significantly decreased, and the number of DC in myocardial tissues was significantly increased, and the levels of serum inflammatory factors were increased significantly. The 14-day cumulative survival rate in VAG539-LPS group was significantly higher than that in the LPS group (55% vs. 15%, P < 0.05). Compared with LPS group, after pretreatment by VAG539, the HR, MAP, LVEF and FS were significantly increased [HR (bpm): 610±25 vs. 556±28, MAP (mmHg, 1 mmHg = 0.133 kPa): 68±6 vs. 42±2, LVEF: 0.48±0.02 vs. 0.30±0.03, FS: (34±3)% vs. (14±2)%, P < 0.05]; the number of DC in myocardial tissue was significantly decreased from 6.5% to 3.7%; the level of serum inflammatory factors were significantly decreased [TNF-α (ng/L): 192.00±25.45 vs. 291.34±23.12, IL-12 (ng/L): 58.44±12.37 vs. 78.43±11.24, IL-6 (ng/L): 46.97±8.12 vs. 149.12±15.45, all P < 0.05]. CONCLUSIONS: Sepsis can cause cardiac dysfunction, and it can play an important role by inhibiting the DC cell function of myocardium and reducing the expression of inflammatory factors.

Impact of the Antibiotic Stewardship Program on Prevention and Control of Surgical Site Infection during Peri-Operative Clean Surgery.

BACKGROUND: Surgical site infections (SSIs) are the leading cause of hospital-acquired infections and are associated with substantial healthcare costs, with increased morbidity and mortality. To investigate the effects of the antibiotic stewardship program on prevention and control of SSI during clean surgery, we investigated this situation in our institution. PATIENTS AND METHODS: We performed a quasi-experimental study to compare the effect before and after the antibiotic stewardship program intervention. During the pre-intervention stage (January 1, 2010 through December 31, 2011), comprehensive surveillance was performed to determine the SSI baseline data. In the second stage (January 1, 2012 through December 31, 2016), an infectious diseases physician and an infection control practitioner identified the surgical patients daily and followed up on the duration of antimicrobial prophylaxis. RESULTS: From January 1, 2010 to December 31, 2016, 41,426 patients underwent clean surgeries in a grade III, class A hospital. The rate of prophylactic antibiotic use in the 41,426 clean surgeries was reduced from 82.9% to 28.0% after the interventions. The rate of antibiotic agents administered within 120 minutes of the first incision increased from 20.8% to 85.1%. The rate at which prophylactic antimicrobial agents were discontinued in the first 24 hours after surgery increased from 22.1% to 60.4%. Appropriate antibiotic selection increased from 37.0% to 93.6%. Prophylactic antibiotic re-dosing increased from 3.8% to 64.8%. The SSI rate decreased from 0.7% to 0.5% (p < 0.05). The pathogen detection rate increased from 16.7% up to 41.8% after intervention. The intensity of antibiotic consumption reduced from 74.9 defined daily doses (DDDs) per 100 bed-days to 34.2 DDDs per 100 bed-days after the interventions. CONCLUSION: Long-term and continuous antibiotic stewardship programs have important effects on the prevention and control of SSI during clean surgery.

Neutrophil Dysfunction in Sepsis.

OBJECTIVE: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. DATA SOURCES: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of "neutrophil function", "neutrophil dysfunction", and "sepsis". STUDY SELECTION: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. RESULTS: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. CONCLUSIONS: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed.