Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified. RESULTS: Meta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection. CONCLUSIONS: This study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.

Tuberculosis combined with Burkitt lymphoma in a kidney transplant recipient: A case report and literature review.

RATIONALE: Tuberculosis (TB) and post-transplant lymphoproliferative disorder are serious complications affecting the long-term survival of kidney transplant recipients (KTRs). Both of complications have overlapping clinical symptoms, signs, and high similar imaging presentation, which make early clinical diagnosis challenging. In this paper, we reported a rare case of post-transplant pulmonary TB combined with Burkitt lymphoma (BL) in KTR. PATIENT CONCERNS: A 20-year-old female KTR presented to our hospital with abdominal pain and multiple nodules throughout the body. DIAGNOSES: TB is diagnosed based on the lung histopathology showed fibrous connective tissue hyperplasia with number of chronic inflammatory changes, localized necrosis, granuloma formation and multinucleated giant cells were seen in the lung tissue. Moreover, lung histopathology specimen tested positive for TB gene. TB The culture for tuberculosis was positive. BL was diagnosed as metastatic after completion of liver and bone marrow biopsy. INTERVENTIONS: After an early diagnosis of TB, the patient received intensification of anti-tubercular therapy. Because the patient was diagnosed with BL, rituximab, cardioprotection, hepatoprotection and alkalinization of urine were added. OUTCOMES: After an early diagnosis of TB, the patient received anti-tubercular therapy and her clinical symptoms and imaging manifestations improved. After the diagnosis of BL was made, the patient's condition progressed rapidly, followed by multi-organ damage and died 3 months later. LESSONS: Therefore, in organ transplant patients, who present with multiple nodules and normal tumor markers, they should be alerted to the possibility of concurrent TB and post-transplant lymphoproliferative disorder, and perfect tests such as Epstein-Barr virus, ß2-microglobulin, lactate dehydrogenase, γ-interferon release test and Xpert Mycobacterium TB/rifampicin test and perform early lesion site biopsy to clarify the diagnosis with a view to improving the prognosis.

Perioperative Risk Factors for Post-operative Pneumonia after Type A Acute Aortic Dissection Surgery.

OBJECTIVE: Type A acute aortic dissection (TAAAD) is a dangerous and complicated condition with a high death rate before hospital treatment. Patients who are fortunate to receive prompt surgical treatment still face high in-hospital mortality. A series of post-operative complications further affects the prognosis. Post-operative pneumonia (POP) also leads to great morbidity and mortality. This study aimed to identify the prevalence as well as the risk factors for POP in TAAAD patients and offer references for clinical decisions to further improve the prognosis of patients who survived the surgical procedure. METHODS: The study enrolled 89 TAAAD patients who underwent surgical treatment in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei province, China from December 2020 to July 2021 and analyzed the perioperative data and outcomes of these patients. Logistic regression analyses were used to identify the risk factors for POP. RESULTS: In the study, 31.5% of patients developed POP. Patients with POP had higher proportions of severe oxygenation damage, pneumothorax, reintubation, tracheotomy, renal replacement therapy, arrhythmia, gastrointestinal bleeding, and longer duration of mechanical ventilation, fever, ICU stay, and length of stay (all with P<0.05). The in-hospital mortality was 2.3%. Smoking, preoperative white blood cells, and intraoperative transfusion were the independent risk factors for POP in TAAAD. CONCLUSION: Patients who underwent TAAAD surgery suffered poorer outcomes when they developed POP. Furthermore, patients with risk factors should be treated with caution.

A predictive model using risk factor categories for hospital-acquired pneumonia in patients with aneurysmal subarachnoid hemorrhage.

Objectives: To identify risk factors for hospital-acquired pneumonia (HAP) in patients with aneurysmal subarachnoid hemorrhage (aSAH) and establish a predictive model to aid evaluation. Methods: The cohorts of 253 aSAH patients were divided into the HAP group (n = 64) and the non-HAP group (n = 189). Univariate and multivariate logistic regression were performed to identify risk factors. A logistic model (Model-Logit) was established based on the independent risk factors. We used risk factor categories to develop a model (Model-Cat). Receiver operating characteristic curves were generated to determine the cutoff values. Areas under the curves (AUCs) were calculated to assess the accuracy of models and single factors. The Delong test was performed to compare the AUCs. Results: The multivariate logistic analysis showed that the age [p = 0.012, odds ratio (OR) = 1.059, confidence interval (CI) = 1.013-1.107], blood glucose (BG; >7.22 mmol/L; p = 0.011, OR = 2.781, CI = 1.263-6.119), red blood distribution width standard deviation (RDW-SD; p = 0.024, OR = 1.118, CI = 1.015-1.231), and Glasgow coma scale (GCS; p < 0.001, OR = 0.710, CI = 0.633-0.798) were independent risk factors. The Model-Logit was as follows: Logit(P) = -5.467 + 0.057 * Age + 1.023 * BG (>7.22 mmol/L, yes = 1, no = 0) + 0.111 * RDW-SD-0.342 * GCS. The AUCs values of the Model-Logit, GCS, age, BG (>7.22 mmol/L), and RDW-SD were 0.865, 0.819, 0.634, 0.698, and 0.625, respectively. For clinical use, the Model-Cat was established. In the Model-Cat, the AUCs for GCS, age, BG, and RDW-SD were 0.850, 0.760, 0.700, 0.641, and 0.564, respectively. The AUCs of the Model-Logit were insignificantly higher than the Model-Cat (Delong test, p = 0.157). The total points from -3 to 4 and 5 to 14 were classified as low- and high-risk levels, respectively. Conclusions: Age, BG (> 7.22 mmol/L), GCS, and RDW-SD were independent risk factors for HAP in aSAH patients. The Model-Cat was convenient for practical evaluation. The aSAH patients with total points from 5 to 14 had a high risk for HAP, suggesting the need for more attention during treatment.

Inhibition of Spleen Tyrosine Kinase Restores Glucocorticoid Sensitivity to Improve Steroid-Resistant Asthma.

BACKGROUND: Regulation or restoration of therapeutic sensitivity to glucocorticoids is important in patients with steroid-resistant asthma. Spleen tyrosine kinase (Syk) is activated at high levels in asthma patients and mouse models, and small-molecule Syk inhibitors such as R406 show potent anti-inflammatory effects in the treatment of immune inflammatory diseases. Several downstream signaling molecules of Syk are involved in the glucocorticoid response, so we hypothesized that R406 could restore sensitivity to dexamethasone in severe steroid-resistant asthma. Objective: To discover the role of the Syk inhibitor R406 in glucocorticoid resistance in severe asthma. Methods: Steroid-resistant asthma models were induced by exposure of C57BL/6 mice to house dust mite (HDM) and ß-glucan and by TNF-α administration to the bronchial epithelial cell line BEAS-2B. We evaluated the role of the Syk inhibitor R406 in dexamethasone (Dex)-insensitive airway inflammation. Pathological alterations and cytokines in the lung tissues and inflammatory cells in BALF were assessed. We examined the effects of Dex or R406 alone and in combination on the phosphorylation of MAPKs, glucocorticoid receptor (GR) and Syk, as well as the transactivation and transrepression induced by Dex in mouse lung tissues and BEAS-2B cells. Results: Exposure to HDM and ß-glucan induced steroid-resistant airway inflammation. The Syk inhibitor R406 plus Dex significantly reduced airway inflammation compared with Dex alone. Additionally, TNF-α-induced IL-8 production in BEAS-2B cells was not completely inhibited by Dex, while R406 markedly promoted the anti-inflammatory effect of Dex. Compared with Dex alone, R406 enhanced Dex-mediated inhibition of the phosphorylation of MAPKs and GR-Ser226 induced by allergens or TNF-α in vivo and in vitro. Moreover, R406 also restored the impaired expression and nuclear translocation of GRα induced by TNF-α. Then, the activation of NF-κB and decreased HDAC2 activity in the asthmatic model were further regulated by R406, as well as the expression of GILZ. Conclusions: The Syk inhibitor R406 improves sensitivity to dexamethasone by modulating GR. This study provides a reference for the development of drugs to treat severe steroid-resistant asthma.

Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis.

BACKGROUND AND PURPOSE: Ferroptosis is closely associated with respiratory diseases; however, the relationship between ferroptosis and neutrophilic asthma remains unknown. This study investigated whether Liproxstatin-1 (Lip-1) affects the progression of neutrophilic asthma by inhibiting ferroptosis and inflammatory response, while dissecting the underlying molecular mechanisms. METHODS: The bronchial epithelial cells (16HBE and BEAS-2B) were administered with lipopolysaccharide (LPS) and interleukin-13 (IL-13) to generate a cell injury model. This cell model was employed to examine the effect of Lip-1 on airway epithelial-associated inflammation and ferroptosis as well as the underlying molecular mechanism. Meanwhile, we evaluated the effects of Lip-1 on neutrophilic asthma and ferroptosis by using the ovalbumin (OVA)/LPS-induced mouse model. RESULTS: Lip-1 reversed the altered expression of ferroptotic regulators (glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and prostaglandin-endoperoxide synthase 2 (PTGS2)), attenuated lipid reactive oxygen species (lipid ROS) and ameliorated cell viability in HBE and BEAS-2B cells administered with LPS and IL-13. Moreover, Lip-1 treatment led to a marked reduction in the expression of IL-33, TSLP, IL-8, IL-6, and HMGB1 in the HBE and BEAS-2B cells. In the meantime, administration with Lip-1 markedly relieved OVA/LPS-induced neutrophilic asthma, as indicated by significant improvement in lung pathological changes, airway mucus secretion, inflammation, and ferroptosis. CONCLUSION: This study provides data suggesting that Lip-1 alleviates neutrophilic asthma in vivo and in vitro through inhibiting ferroptosis, perhaps providing a new strategy for neutrophilic asthma treatment.

The α7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Improves Bacterial Clearance via Regulation of Monocyte Recruitment and Activity in Polymicrobial Septic Peritonitis.

The cholinergic anti-inflammatory pathway has been identified as an effective pathway to modify inflammatory responses. Here, we verified that delayed administration with a selective α7nAChR agonist GTS-21 enables a more efficient elimination of the offending pathogens, diminished inflammatory response and organ injury, and improved survival rates in the polymicrobial septic peritonitis model. We illustrated that the improved bacterial clearance upon GTS-21 stimulation was accompanied by enhanced recruitment of monocytes into the peritoneal cavity and simultaneously increased phagocytic activity and iNOS expression of these recruited monocytes. Mechanically, splenectomy prior to administration of GTS-21 attenuated the recruitment of monocytes into the peritoneal cavity and abolished the protective benefits of GTS-21 treatment. Meanwhile, GTS-21 administration accelerates the deployment of splenic monocytes during septic peritonitis. Collectively, these data suggested that appropriate selective pharmacological α7nAChR activation promotes monocytes trafficking in a spleen-dependent manner and upregulates the antibacterial activity of recruited monocytes during septic peritonitis, which may be utilized as a promising therapeutic modality for patients suffering from septic peritonitis.

Atomic-scale probing of heterointerface phonon bridges in nitride semiconductor.

Interface phonon modes that are generated by several atomic layers at the heterointerface play a major role in the interface thermal conductance for nanoscale high-power devices such as nitride-based high-electron-mobility transistors and light-emitting diodes. Here we measure the local phonon spectra across AlN/Si and AlN/Al interfaces using atomically resolved vibrational electron energy-loss spectroscopy in a scanning transmission electron microscope. At the AlN/Si interface, we observe various interface phonon modes, of which the extended and localized modes act as bridges to connect the bulk AlN modes and bulk Si modes and are expected to boost the phonon transport, thus substantially contributing to interface thermal conductance. In comparison, no such phonon bridge is observed at the AlN/Al interface, for which partially extended modes dominate the interface thermal conductivity. This work provides valuable insights into understanding the interfacial thermal transport in nitride semiconductors and useful guidance for thermal management via interface engineering.

ER stress and its PERK branch enhance TCR-induced activation in regulatory T cells.

Although accumulating evidence indicates participation of endoplasmic reticulum (ER) stress pathway or the unfolded protein response (UPR) in immunity, there still exists little information linking ER stress to regulatory T cells (Tregs). To evaluate the potential contribution of the UPR, we tested the effects of thapsigargin (TG), an ER stress inducer, on the function of Tregs. Here we reported that TG stimulation induced the up-regulation of the endoplasmic reticulum (ER)-stress chaperon Glucose-Regulated Protein 78 (GRP78), which is a master regulator of the UPR, the phosphorylation of eukaryotic initiation factor 2 alpha (elF2α) and the induction of activating transcription factor 4 (ATF4), which are both protein kinase R (PKR)-like ER kinase (PERK) downstream targets in Tregs. Simultaneously, we demonstrated that, under ER stress conditions, Tregs presented enhanced functional activity upon TCR stimulation, as illustrated with forkhead box transcription factor (Foxp3) expression, interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) production and suppressive functional analysis. Notably, pretreatment with GSK2656157, a potent and selective PERK inhibitor, markedly diminished the TG-induced hyperresponsiveness of Tregs upon T cell antigen receptor (TCR) stimulation. Therefore, our findings illustrated the inter-connection and coordination of the evolutionarily conserved ER stress response and TCR signaling in Tregs and uncover a critical new role of the PERK branch of UPR in the regulation of Tregs function.

One delayed diagnosis of paragonimiasis case and literature review.

Human paragonimiasis has been appearing all over the world due to increased human migration, international travel, and worldwide food trading. However, delayed and missed diagnosis rates are also increasing due to atypical clinical manifestations and the lack of disease understanding by clinical workers. We describe the case of a 43-year-old man, who was hospitalized with cough and chest pain for two months. Chest computed tomography (CT) revealed bilateral emphysema, left pleural effusion, and bilateral atelectasis. The hypereosinophilia gave us a clue; ultimately, the diagnosis of paragonimiasis was made through a diet history and a positive result of serum Paragonimus sp. immunoglobulin (Ig) G antibody. Moreover, 27 misdiagnosed paragonimiasis cases in the past decade have been reported. We draw conclusions by summarizing their characteristics for suspicious eosinophilic paragonimiasis patients; we should inquire diet history carefully, test serum IgG antibodies, and try to detect eggs. Once diagnosed, praziquantel is preferred for treatment.

The Essential Involvement of the Omentum in the Peritoneal Defensive Mechanisms During Intra-Abdominal Sepsis.

Although the abilities of the omentum to alleviate inflammation and prevent infection have been revealed over the past decades, the underlying mechanisms remain largely unelucidated. Here, we demonstrated that the mortality of mice exposed to cecal ligation and puncture (CLP) and omentectomy was remarkably increased compared to those treated with CLP alone. Moreover, the efficacy of the omentum was associated with an impairment in intraperitoneal bacterial clearance together with an increase in the expression of proinflammatory cytokines. Besides, in response to peritoneal infections, the size and quantity of the omental milky spots (MSs) were increased tremendously and they also support innate-like B1 cell responses and local IgM production in the peritoneal cavity. Furthermore, not only the migration but also the functional activities of neutrophils were diminished in the absence of the omentum. These data collectively show that the omentum contributes more to peritoneal immune responses during septic peritonitis than has heretofore been recognized. Thus, harnessing the function of MS-containing omentum to increase its protective effectiveness may exert important biological and therapeutic implications for the control of intra-abdominal infections.

[Research progress of exploring the treatment of sepsis based on cholinergic anti-inflammatory pathway].

The cholinergic anti-inflammatory pathway (CAP) is an important neuroimmunomodulatory mechanism that innervates the spleen through vagus nerve efferent and splenic nerve relay, and acts on macrophages by transforming adrenergic stimulation into cholinergic signal by spleen T cells, which plays an anti-inflammatory effect, and maintains the balance of inflammatory response. Due to the critical role of the imbalance of pro-inflammatory and anti-inflammatory responses in the physiological process of sepsis, regulating the activity of the CAP has become an important focus in the treatments of sepsis. Based on the understanding of the CAP, vagus nerve stimulation, drug agonists mimicking cholinergic signals, and acupuncture are currently applied in the research and exploration of sepsis treatment. This article summarizes the recent progress and prospects of the CAP mechanism, biological effects, and application in sepsis treatment.

Application of acid-fast staining combined with GeneXpert MTB/RIF in the diagnosis of non-tuberculous mycobacteria pulmonary disease.

OBJECTIVE: To evaluate the clinical diagnostic value of positive acid-fast staining combined with negative GeneXpert MTB/RIF in the diagnosis of non-tuberculous mycobacteria pulmonary disease (NTM-PD). METHODS: A total of 133 inpatients with confirmed NTM-PD were included consecutively between January 1, 2018 and December 31, 2019, at Tongji Hospital and Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, in Wuhan, China. One hundred patients with confirmed pulmonary tuberculosis (PTB) were randomly included as the control group. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of positive acid-fast staining combined with a negative GeneXpert MTB/RIF result were 51.13% (95% confidence interval (CI) 42.52-59.73%), 97.00% (95% CI 93.60-100.40%), 95.78% (95% CI 90.98-100.57%), and 59.88% (95% CI 52.25-67.51%), respectively. When subjects were limited to patients with positive acid-fast staining, the sensitivity of a negative GeneXpert MTB/RIF result was 88.31% (95% CI 80.97-95.65%). When acid-fast staining was conducted ≥3 times, the sensitivity of this combination diagnosis method increased to 61.67% (95% CI 49.00-74.33%). CONCLUSIONS: Positive acid-fast staining combined with a negative GeneXpert MTB/RIF result could be an effective and time-saving method for the diagnosis of NTM-PD.

Autocrine Regulation of Interleukin-3 in the Activity of Regulatory T Cells and its Effectiveness in the Pathophysiology of Sepsis.

Regulatory T cells (Tregs) play a crucial role in modulating the inflammatory response and participated in sepsis-related immune dysfunctions. However, little is known about the regulatory mechanisms by which Tregs are kept in check during immune responses. Here, we verified the simultaneous expression of interleukin-3 (IL-3) and its receptor (IL-3R) in Tregs. Then, by modulation of IL-3 expression via lentiviral transduction-mediated small interfering RNA, we demonstrated that IL-3 negatively regulated Tregs activity via an autocrine mechanism. Furthermore, we found that anti-IL-3 antibody treatment significantly diminished inflammatory cytokines and organ injury, and improved survival in septic mice, which was associated with enhanced Treg percentage and function. Collectively, these results suggest that IL-3 negatively regulates the activity of Tregs in a previously unrecognized autocrine manner, and plays an important role in the excessive inflammatory response in sepsis, which might be utilized as a therapeutic strategy for the treatment of complications in sepsis.

A Transcriptional Sequencing Analysis of Islet Stellate Cell and Pancreatic Stellate Cell.

BACKGROUND: Our previous studies have shown that islet stellate cell (ISC), similar to pancreatic stellate cell (PSC) in phenotype and biological characters, may be responsible for the islet fibrosis in type 2 diabetes. To further identify the differences between PSC and ISC and for better understanding of the physiological function of ISC, we employed genome-wide transcriptional analysis on the PSCs and ISCs of Wistar rats. METHOD: PSCs and ISCs from each rat were primarily cultured at the same condition. Genome-wide transcriptional sequence of stellate cells was generated. The identified differentially expressed genes were validated using RT-PCR. RESULTS: 32 significant differentially expressed genes between PSCs and ISCs were identified. Moreover, collagen type 11a1 (COL11A1), was found to be expressed 2.91-fold higher in ISCs compared with PSCs, indicating that COL11A1 might be a potential key gene modulating the differences between PSC and ISC. CONCLUSIONS: Our study identified and validated the differences between PSC and ISC in genome-wide transcriptional scale, confirming the assumption that ISC and PSC are similar other than identical. Moreover, our data might be instrumental for further investigation of ISC and islet fibrosis, and some differential expressed genes may provide an insight into new therapeutic targets for type 2 diabetes.

Improving the emission efficiency of MBE-grown GaN/AlN QDs by strain control.

The quantum-confined stark effect induced by polarization has significant effects on the optical properties of nitride heterostructures. In order to improve the emission efficiency of GaN/AlN quantum dots [QDs], a novel epitaxial structure is proposed: a partially relaxed GaN layer followed by an AlN spacer layer is inserted before the growth of GaN QDs. GaN/AlN QD samples with the proposed structure are grown by molecular beam epitaxy. The results show that by choosing a proper AlN spacer thickness to control the strain in GaN QDs, the internal quantum efficiencies have been improved from 30.7% to 66.5% and from 5.8% to 13.5% for QDs emitting violet and green lights, respectively.