Peritoneal dialysis-related peritonitis caused by Pseudomonas species: Insight from a post-millennial case series.

Pseudomonas peritonitis is a serious complication of peritoneal dialysis (PD). However, the clinical course of Pseudomonas peritonitis following the adoption of international guidelines remains unclear.We reviewed the clinical course and treatment response of 153 consecutive episodes of PD peritonitis caused by Pseudomonas species from 2001 to 2015.Pseudomonas peritonitis accounted for 8.3% of all peritonitis episodes. The bacteria isolated were resistant to ceftazidime in 32 cases (20.9%), and to gentamycin in 18 cases (11.8%). In 20 episodes (13.1%), there was a concomitant exit site infection (ESI); in another 24 episodes (15.7%), there was a history of Pseudomonas ESI in the past. The overall primary response rate was 53.6%, and complete cure rate 42.4%. There was no significant difference in the complete cure rate between patients who treated with regimens of 3 and 2 antibiotics. Amongst 76 episodes (46.4%) that failed to respond to antibiotics by day 4, 37 had immediate catheter removal; the other 24 received salvage antibiotics, but only 6 achieved complete cure.Antibiotic resistance is common amongst Pseudomonas species causing peritonitis. Adoption of the treatment guideline leads to a reasonable complete cure rate of Pseudomonas peritonitis. Treatment with three antibiotics is not superior than the conventional two antibiotics regimen. When there is no clinical response after 4 days of antibiotic treatment, early catheter removal should be preferred over an attempt of salvage antibiotic therapy

Asymptomatic fluid overload predicts survival and cardiovascular event in incident Chinese peritoneal dialysis patients.

BACKGROUND:Fluid overload is common among asymptomatic peritoneal dialysis (PD) patients. We aim to determine the prevalence and prognostic significance of fluid overload, as measured by bioimpedance spectroscopy, in asymptomatic incident PD patients. METHODS:We performed a single-center study on 311 incident PD patients. Volume status was represented by the volume of overhydration (OH), OH/extracellular water (ECW) ratio, ECW/total body water (TBW) ratio, and ECW to intracellular water (ICW) ratio (E:I ratio). Patient survival, technique survival and cardiovascular event-free survival were determined. RESULTS:The median period of follow up was 27.3 months. Fluid overload was present in 272 patients (87.5%) when defined as OH volume over 1.1L. All hydration parameters significantly correlated with Charlson Comorbidity Index, and inversely with total Kt/V, and serum albumin. Multivariate cause-specific Cox analysis showed that volume status independently predicted patient survival; every 0.1 unit increase in E:I ratio was associated with 24.5% increase in all-cause mortality (adjusted cause-specific hazard ratio [ACSHR] 1.245, p = 0.002). Hydration status was also an independent predictor of cardiovascular event-free survival after excluding hospital admission for congestive heart failure; each 0.1 unit increase in E:I ratio was associated with 18.7% decrease in cardiovascular event-free survival (ACSHR 1.187, p = 0.011). In contrast, hydration parameters were not associated with technique survival. CONCLUSIONS:Fluid overload is common in asymptomatic incident PD patients and is a strong predictor of patient survival and cardiovascular event. The impact of bioimpedance spectroscopy-guided fluid management on the outcome of PD patients deserves further study

Treatment of Enterococcal Peritonitis in Peritoneal Dialysis Patients by Oral Amoxicillin or Intra-Peritoneal Vancomcyin: a Retrospective Study

Background/Aims: Enterococcal peritonitis in peritoneal dialysis (PD) patients is associated with a high complication rate. The optimal treatment regimen of PD-related enterococcal peritonitis is controversial. The latest international guideline recommends intra-peritoneal (IP) vancomycin. Although ampicillin is often effective for systemic enterococcal infections, they have little in vitro activity when added to common PD solutions. Since oral amoxicillin achieves therapeutic drug level in the peritoneal cavity, we explore the efficacy of oral amoxicillin for enterococcal peritonitis. Methods: We studied 105 episodes of enterococcal peritonitis over 20 years in our unit; 43 (41.0%) were treated with oral amoxicillin, and 62 (59.0%) with IP vancomycin. Their clinical outcome was reviewed. Result: The overall primary response rate to oral amoxicillin and IP vancomycin was 76.4% and 85.5%, respectively (p = 0.3). The complete cure rate of oral amoxicillin and IP vancomycin was 55.8% and 54.8%, respectively (p = 0.8). When the 5 episodes of ampicillin-resistant Enterococcus episodes were excluded, the primary response rate and complete cure rate of oral amoxicillin were 86.8% and 63.2%, respectively. Conclusion: Oral amoxicillin has an excellent primary response rate and complete cure rate for PD-related peritonitis episodes caused by Enterococcus species, indicating that oral amoxicillin is a valid and convenient therapeutic option for enterococcal peritonitis episodes

Relationship between serial serum neutrophil-lymphocyte ratio, cardiovascular mortality, and all-cause mortality in Chinese peritoneal dialysis patients

Background It is believed that the excessive cardiovascular (CV) burden of patients on peritoneal dialysis (PD) is closely associated with chronic inflammation. Neutrophil-lymphocyte ratio (NLR) is an inflammatory marker that was shown to correlate with CV outcomes. However, little is known about the significance of serial monitoring of serum NLR. We aimed to determine the prognostic value of serial NLR on all-cause mortality and CV mortality in PD patients. Methods Serial measurement of NLR was obtained from 225 incident PD patients in a single center, with each measurement one year apart. Patients were divided into two groups (‘high’ versus ‘low’) by the median value of NLR. The primary and secondary outcome measure was all-cause and CV mortality respectively. Results After a median of follow up for 43.9 months, patients with lower baseline NLR demonstrated a higher survival rate (p=0.01). Patients with persistently high NLR values on serial measurement had the lowest survival rate (p=0.03). Multivariate Cox regression showed that this group of patients had significantly higher all-cause mortality (HR 1.74, 95%CI 1.09 to 2.79, p=0.02). However, the NLR failed to demonstrate a statistically significant relationship with CV mortality. Conclusions While baseline NLR was an independent predictor of all-cause mortality in PD patients, persistent elevation in NLR appeared to further amplify the risk. Regular monitoring of serial serum NLR may enable early identification of patients who are at risk of adverse outcome

Hematopoietic Transcription Factor RUNX1 is Essential for Promoting Macrophage–Myofibroblast Transition in Non‐Small‐Cell Lung Carcinoma

Abstract Macrophage‐myofibroblast transition (MMT) is a newly discovered pathway for mass production of pro‐tumoral cancer‐associated fibroblasts (CAFs) in non‐small cell lung carcinoma (NSCLC) in a TGF‐β1/Smad3 dependent manner. Better understanding its regulatory signaling in tumor microenvironment (TME) may identify druggable target for the development of precision medicine. Here, by dissecting the transcriptome dynamics of tumor‐associated macrophage at single‐cell resolution, a crucial role of a hematopoietic transcription factor Runx1 in MMT formation is revealed. Surprisingly, integrative bioinformatic analysis uncovers Runx1 as a key regulator in the downstream of MMT‐specific TGF‐β1/Smad3 signaling. Stromal Runx1 level positively correlates with the MMT‐derived CAF abundance and mortality in NSCLC patients. Mechanistically, macrophage‐specific Runx1 promotes the transcription of genes related to CAF signatures in MMT cells at genomic level. Importantly, macrophage‐specific genetic deletion and systemic pharmacological inhibition of TGF‐β1/Smad3/Runx1 signaling effectively prevent MMT‐driven CAF and tumor formation in vitro and in vivo, representing a potential therapeutic target for clinical NSCLC

LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression

Transforming growth factor-β (TGF-β) is a crucial pathogenic mediator of inflammatory diseases. In tissue fibrosis, TGF-β regulates the pathogenic activity of infiltrated immunocytes and promotes extracellular matrix production via de novo myofibroblast generation and kidney cell activation. In cancer, TGF-β promotes cancer invasion and metastasis by enhancing the stemness and epithelial mesenchymal transition of cancer cells. However, TGF-β is highly pleiotropic in both tissue fibrosis and cancers, and thus, direct targeting of TGF-β may also block its protective anti-inflammatory and tumor-suppressive effects, resulting in undesirable outcomes. Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in TGF-β-driven tissue fibrosis and cancer progression with a high cell-type and disease specificity, serving as an ideal target for therapeutic development. In this review, the mechanism and translational potential of TGF-β-associated lncRNAs in tissue fibrosis and cancer will be discussed

Summary of clinical outcome.

<p>(Abbreviations: TKR, Tenckhoff catheter removal; PD, peritoneal dialysis).</p

Changes in peritoneal transport, nutritional status, and dialysis adequacy before and after the episode of <i>Pseudomonas</i> peritonitis^*.

<p>Changes in peritoneal transport, nutritional status, and dialysis adequacy before and after the episode of <i>Pseudomonas</i> peritonitis^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0196499#t003fn001" target="_blank">*</a>}.</p

Baseline characteristics of the patients^*.

<p>Baseline characteristics of the patients^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0196499#t001fn001" target="_blank">*</a>}.</p