Effects of driving pressure-guided ventilation by individualized positive end-expiratory pressure on oxygenation undergoing robot-assisted laparoscopic radical prostatectomy: a randomized controlled clinical trial.

PURPOSE: Patients with robot-assisted laparoscopic radical prostatectomy (RALP) need to be placed in Trendelenburg position, which results in cranial displacement of the diaphragm and decreases functional residual capacity and pulmonary compliance. Positive end-expiratory pressure (PEEP) can increase ventilation in the dorsal area, reduce the occurrence of atelectasis and improve oxygenation. However, due to individual differences, inappropriate PEEP will cause lung injury and even hemodynamic instability. Therefore, our study is to evaluate the efficacy of individualized PEEP in RALP. METHODS: We randomly recruited 48 patients and divided them into driving pressure-guided individualized PEEP group (P group, individualized PEEP) or traditional lung-protective ventilation strategy group (C group, tidal volume 8 mL/kg combined with PEEP of 5cmH2O). The primary outcome was the PaO2/FiO2 before extubation. The secondary outcomes included individualized PEEP values in the P group, the results of arterial blood gas analysis, respiratory mechanics parameters and vital sign parameters. Other measurements included intraoperative vasoactive drug dosage, length of stay, postoperative SpO2, leukocyte count, temperature, serum inflammatory factors and soluble receptor for advanced glycation end products (sRAGE). RESULTS: Individualized PEEP improved the PaO2/FiO2 before extubation (P = 0.034) and decreased driving pressure (P = 0.011). The PEEP valued in the P group was 14 [10-14] cmH2O. The lung compliance of the P group was significantly higher than that in the C group (P = 0.013). There was no significant difference in other measurements. CONCLUSIONS: Individualized PEEP could improve PaO2/FiO2 in patients who underwent RALP and do not increase the dosage of intraoperative vasoactive drug and the release of inflammatory factors. TRIAL REGISTRATION: www.chictr.org.cn (registration no. ChiCTR2100047271).

Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study.

BACKGROUND: Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China. METHODS: In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected. RESULT: Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883-48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066-31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663-46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228-6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226-32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI. CONCLUSION: In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.

Roseomonas mucosa infective endocarditis in patient with systemic lupus erythematosus: case report and review of literature.

BACKGROUND: Roseomonas mucosa, as a Gram-negative coccobacilli, is an opportunistic pathogen that has rarely been reported in human infections. Here we describe a case of bacteremia in an infective endocarditis patient with systemic lupus erythematosus (SLE). CASE PRESENTATIONS: A 44-year-old female patient with SLE suffered bacteremia caused by Roseomonas mucosa complicated with infective endocarditis (IE). The patient started on treatment with piperacillin-tazobactam and levofloxacin against Roseomonas mucosa, which was switched after 4 days to meropenem and amikacin for an additional 2 weeks. She had a favorable outcome with a 6-week course of intravenous antibiotic therapy. DISCUSSION AND CONCLUSIONS: Roseomonas mucosa is rarely reported in IE patients; therefore, we report the case in order to improve our ability to identify this pathogen and expand the range of known bacterial causes of infective endocarditis.

Immortalized Bone Mesenchymal Stromal Cells With Inducible Galanin Expression Produce Controllable Pain Relief in Neuropathic Rats.

Management of chronic pain is one of the most difficult problems in modern practice. Grafted human telomerase reverse transcriptase-immortalized bone marrow mesenchymal stromal cells (hTERT-BMSCs) with inducible galanin (GAL) expression have been considered to be a potentially safe and controllable approach for the alleviation of chronic pain. Therefore, in this study, we aimed to assess the feasibility of hTERT-BMSCs/Tet-on/GAL cells secreting GAL under the transcriptional control of doxycycline (Dox) for controllable pain relief. After transplanted into the subarachnoid space of neuropathic rats induced by spared nerve injury of sciatic nerve, their analgesic actions were investigated by behavioral tests. The results showed that the pain-related behaviors, mechanical allodynia, and thermal hyperalgesia were significantly alleviated during 1 to 7 weeks after grafts of hTERT-BMSCs/Tet-on/GAL cells without motor incoordination. Importantly, these effects could be reversed by GAL receptor antagonist M35 and regulated by Dox induction as compared with control. Moreover, the GAL level in cerebrospinal fluid and spinal GAL receptor 1 (GalR1) expression were correlated with Dox administration, but not GAL receptor 2 (GalR2). Meanwhile, spinal protein kinase Mζ (PKMζ) expression was also inhibited significantly. Taken together, these data suggest that inducible release of GAL from transplanted cells was able to produce controllable pain relief in neuropathic rats via inhibiting the PKMζ activation and activating its GalR1 rather than GalR2. This provides a promising step toward a novel stem cell-based strategy for pain therapy.

Cell atavistic transition: Paired box 2 re-expression occurs in mature tubular epithelial cells during acute kidney injury and is regulated by Angiotensin II.

The regeneration of tubular epithelial cells (TECs) after acute kidney injury (AKI) is crucial for the recovery of renal structure and function. The mechanism by which quiescent TECs re-obtain a potential to regenerate remains unknown. In this study, we observed a transient re-expression of embryonic gene Paired box 2 (Pax2) in adult rat TECs in vivo during ischemia-reperfusion induced AKI and most Pax2 positive TECs co-expressed kidney injury molecule-1 (KIM-1), a tubular injury marker. The re-expression of Pax2 was accompanied by increased levels of intrarenal Angiotensin II, which is a crucial injury factor of AKI. Furthermore, we also found a temporary re-expression of Pax2 in NRK-52E cells under the stimulation of Angiotensin II. This stimulatory effect could be blocked by PD123319 (Angiotensin II type 2 receptor (AT2R) inhibitor) and AG490 (Janus Kinase 2 (JAK2) inhibitor). As Pax2 is essential for the phenotypic conversion from mesenchymal stem cells to TECs during kidney development, we proposed that the re-expression of Pax2 in mature TECs may be an indicator of "atavistic" transition which mimics but reverses the processes of development of TECs. This could be proved by that a progenitor marker, CD24, was also found to be transiently expressed shortly after the expression of Pax2 in NRK-52E cells stimulated with Angiotensin II. The expression of CD24 was also suppressed by PD123319 and AG490. Moreover, knockdown of Pax2 by RNA interference could significantly reduce the expression of CD24 in NRK-52E cells stimulated with Angiotension II. Those findings suggest that mature TECs can trans-differentiate into progenitor-like cells by "atavistic transition", which may participate in the recovery of tissue structure and Pax2 may play a pivotal role in this process. That might have important implications for further understanding of tubular regeneration after injury.

Escherichia coli Peritonitis in peritoneal dialysis: the prevalence, antibiotic resistance and clinical outcomes in a South China dialysis center.

INTRODUCTION: Escherichia coli (E. coli) peritonitis is a frequent, serious complication of peritoneal dialysis (PD). The extended-spectrum ß-lactamase (ESBL)-producing E. coli peritonitis is associated with poorer prognosis and its incidence has been on continuous increase during the last decades. However, the clinical course and outcomes of E. coli peritonitis remain largely unclear. METHODS: All of the E. coli peritonitis episodes that occurred in our dialysis unit from 2006 to 2011 were reviewed. The polymicrobial episodes were excluded. RESULTS: In total, ninety episodes of monomicrobial E. coli peritonitis occurred in 68 individuals, corresponding to a rate of 0.027 episodes per patient-year. E. coli was the leading cause (59.2%) of monomicrobial gram-negative peritonitis. ESBL-producing strains accounted for 35.5% of E. coli peritonitis. The complete cure rate and treatment failure rate of E. coli peritonitis were 77.8% and 10.0% respectively. Patients with preceding peritonitis had a higher risk of ESBL production as compared to those without peritonitis history [odds ratio (OR): 5.286; 95% confidence interval (CI): 2.018 - 13.843; p = 0.001]. The risk of treatment failure was significantly increased when the patient had a baseline score of Charlson Comorbidity Index (CCI) above 3 (OR: 6.155; 95% CI: 1.198 - 31.612; p = 0.03), or had diabetes mellitus (OR: 8.457; 95% CI: 1.838 - 38.91; p = 0.006), or hypoalbuminemia (≤ 30g/l) on admission (OR: 13.714; 95% CI: 1.602 - 117.428; p = 0.01). Prolonging the treatment course from 2 to 3 weeks or more reduced the risk of relapse and repeat significantly (p < 0.05). CONCLUSIONS: E. coli peritonitis remains a common complication of PD. The clinical outcomes of E. coli peritonitis are relatively favorable despite the high ESBL rate. A history of peritonitis is associated with increased risk for ESBL development. The severity of baseline comorbidities, the presence of diabetes mellitus and hypoalbuminemia at admission are associated with poor outcomes.

Glucocorticoid receptor auto-upregulation and its relation with glucocorticoid sensitivity in idiopathic nephrotic syndrome.

BACKGROUND: Resistance to glucocorticoid (GC) treatment is a significant clinical problem in many diseases. Most effects of GC are mediated by glucocorticoid receptor (GR). Multiple promoters have been found in GR gene, which results in different exons 1 s. In human leukemia cell lines, GC response is thought to be related with promoter usage and auto-upregulation of GR. In this study, we investigated whether GR could be auto-induced in peripheral blood mononuclear cells (PBMCs) and whether an inability to upregulate the GR is related with GC resistance in idiopathic nephrotic syndrome (INS). METHODS: Reverse transcription-PCR was applied to measure the mRNA expression of GR transcripts (GR exons 1A, 1B, 1C, and GR), and real-time PCR was used to confirm these results. GR protein expression was analyzed by Western blot. RESULTS: Following GC treatment, both GR exon 1A and GR in PBMCs were increased in vitro, while GR exons 1B and 1C showed no significant changes. In patients with INS, the glucocorticoid-sensitive group expressed more GR exon 1A and less GR exon 1C than the glucocorticoid-resistant group, but the total GR showed no significant difference. CONCLUSIONS: GR is auto-induced in PBMCs in vitro and GR promoter 1A is involved in this mechanism; however the auto-upregulation of GR is not related with glucocorticoid response in patients with INS.

Epigenetic programming of diverse glucocorticoid response and inflammatory/immune-mediated disease.

Glucocorticoid plays a fundamental role in maintaining immune homeostasis. Resistance to glucocorticoids is a potential etiology of inflammatory/immune-mediated disease. Most of the glucocorticoid effects are mediated by glucocorticoid receptor (GR), which has a complicated promoter region with multiple promoters. Studies have found that the methylation pattern of GR promoter is highly individual, which may contribute to the diverse glucocorticoid responds. Early life is a critical time for epigenetic programming of the body in which methylation imprints are established. Here we propose a hypothesis that connects the adverse early life events and the development of inflammatory/immune-mediated disease through an epigenetic mechanism, the methylation of GR gene.