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.

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.

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.

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.