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Abstract

Background

Adjuvant trastuzumab improved overall survival and reduced the risk for disease recurrence in women with breast cancers, because of its potential cardiotoxicity, careful monitoring of left ventricular (LV) function during treatment is required.

Methods

This study investigates, whether myocardial strain imaging and level of N-terminal pro-brain natriuretic peptide (NT-pro BNP) could predict subsequent reduction in LVEF in breast cancer patients received adjuvant trastuzumab. 61 women with pathologically proven breast cancer HER-2 positive received AC (Doxorubicin–Cyclophosphamide) for 4 cycles, followed by paclitaxel with Trastuzumab were enrolled. Clinical, conventional echocardiographic parameters, myocardial strain imaging [global longitudinal peak systolic strain (GLS), radial and circumferential systolic strain] and level of NT pro-BNP were measured at baseline, after 3, 6, 9 and 12 months of trastuzumab therapy.

Results

Of 61 patients, 18 patients (29.5%) developed trastuzumab-induced cardiomyopathy (CM) at 6 and 9 months of therapy (LVEF declines ≥ 10%), GLS and radial strain significantly decreased in CM group at 3 months of trastuzumab treatment, the value of GLS at 3 months was the strongest predictors of cardiotoxicity its area under the curve (AUC 0.98) with an optimal cut-off for GLS (− 18%) having 92.5% sensitivity and 83% specificity. NT-pro BNP levels were not predictive of later trastuzumab-induced cardiac dysfunction.

Conclusion

Myocardial strain imaging has been able to predict pre-clinical changes in LV systolic function and GLS is an independent early predictor of subsequent reduction in EF in breast cancer patients treated with trastuzumab.

Keywords

Breast cancer Trastuzumab Cardiotoxicity Myocardial strain

Acute Renal Failure Following Near-Drowning

Posted by Y Gorelik, S Darawshi, H Yaseen, et al. on 2018-08-21 23:22:55

Introduction

Acute kidney injury associated with near-drowning (ND-AKI) has rarely been reported and its incidence among survivors is unknown. A patient with AKI and urine biomarkers indicating tubular injury led us to assess the occurrence and clinical characteristics of ND-AKI and to evaluate possible causative mechanisms.

Methods

We evaluated medical records of patients rescued from near-drowning in the Mediterranean Sea and treated in a tertiary-level medical center during 2000 to 2017.

Results

Ninety-five patients with the diagnosis of near-drowning in seawater were treated. Forty-two of these patients (43%) developed ND-AKI and 17 (18%) were classified as AKI Kidney Disease: Improving Global Outcomes stages 2 to 3. ND-AKI was associated with the need for resuscitation and mechanical ventilation, with the calculated seawater volume ingestion (extrapolated from rising plasma sodium) and with the degree of acidemia, lactemia, and ventilatory failure. This series and 28 additional published cases of ND-AKI in the literature showed an overall male predisposition.

Conclusion

AKI is a common complication of near-drowning and is associated with increased in-hospital mortality. Data analysis suggests a predominant role of hypoxic tubular injury due to systemic hypoxemia in ND-AKI, combined with intense sympathetic activity (reflected by tachyarrhythmias, hyperglycemia, and relative hypokalemia) and increased oxygen expenditure for intensified distal tubular sodium transport. Androgen-related reduced renal vasodilatory capacity may explain male gender predominance.

Abstract

Background

Nicotine is an important factor in the pathogenesis of renal injury in smokers.

Purpose

The purpose of the present study was to investigate the renoprotective effect of Spirulina platensis extract (SP) against chronic nicotine administration in rats.

Methods

Nicotine intoxication was induced with 0.5 mg/kg BW. Rats received 500 mg SP/kg BW by gastric gavage over 4 weeks.

Results

Our data revealed that nicotine induced renal dysfunction manifested by significant abnormal levels of kidney function markers (creatinine and urea) accompanied by increased levels of oxidative stress biomarker (malondialdehyde) and inflammatory markers (nitric oxide, Interleukin-6 and tumor necrosis factor-α) while antioxidant status as glutathione level and glutathione S-transferase activity were found to be decreased significantly as compared with controls. It is worthy to note that nicotine toxicity induced significant increments in the protein expression levels of nuclear factor kappa B as well as caspase-3. Histopathological observations showed tubular necrosis and congestion in the endothelial lining glomerular tuft and epithelial lining renal tubules with nicotine intoxication. Interestingly, our data demonstrated that SP supplementation significantly improved the nicotine-induced kidney dysfunction, alleviated the induced-lipid peroxidation, inflammatory, apoptotic protein markers, and boosted the enzymatic/non-enzymatic antioxidants. Moreover, it attenuated the nicotine-induced histopathological alterations of the kidney architecture.

Conclusion

Thus, it is tempting to recommend dietary approaches with Spirulina platensis extract for smokers to minimize the deleterious effect of chronic nicotine consumption and exposure-related problems towards kidney injury via its antioxidant, anti-inflammatory and antiapoptotic properties.

Summary

Gastro-esophageal reflux (GER) is common in ventilated patients and is a cause of ventilator associated pneumonia (VAP). The novel persistaltic feeding tube (PFT) uses simulated peristalsis to seal the esophagus to fluid moving in a retrograde manner, whilst allowing normal drainage of fluid and secretions moving in an ante-grade manner. This study describes the first trial of the PFT in ventilated patients.

Methods

There were 10 subjects in the treatment (PFT) group and 10 patients in the control group, who had all undergone elective cardiac surgery and were ventilated in the intensive care unit (ICU) afterwards. The PFT was placed on admission to the ICU. In the control group a standard nasogastric tube (NGT) was inserted. Specimens were collected by suctioning from the oropharynx and from above the tracheal tube balloon every hour and from the trachea twice per 8 h shift. Samples were analyzed by ELISA for Pepsin A, as a marker for secretions of gastric origin. Esophageal pressure monitoring (as a measure of pleural pressure), which is an intrinsic ability of the PFT device, was also noted throughout the study – for future integration in mechanical ventilation strategies.

Results

The two groups were comparable with regard to demographics and duration of ventilation. There was a larger number of specimens positive for Pepsin A in the control group in the oropharynx (p < 0.0001) and above the ETT cuff (p = 0.0001), but not in the trachea (p = 0.0603), using the Wald Chi-squared test. However, when comparing mean concentrations of Pepsin at the three sites, there was a statistically higher concentration in the control group in the oropharynx, above the ETT and in the trachea, compared to the PFT group.

Conclusion

The PFT reduced the amount of GER in ventilated patients. A larger study is required to determine whether this translates to a reduction in VAP.

Australian New Zealand Clinical Trials Registry (ANZCTR)

ACTRN12618000669291.

ABSTRACT

Kefir is a fermented product from yeast and lactic acid bacteria, and has been associated with various health benefits including relieving inflammatory bowel disease. Recently, it has been shown that gram-positive bacteria produce extracellular vesicles (EV). The EV could be appearing as potentially important mediators of cell to cell interaction. In this study, we explored the role of kefir grain Lactobacillus-derived EV in modulating inflammation responses via alleviating the production of inflammatory cytokines in tumor necrosis factor-alpha (TNF-alpha)-induced inflammation in Caco-2 cells and the 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease mouse model. Kefir-derived Lactobacillus EV were isolated by ultracentrifugation of the culture medium of 3 different kefir-derived strains (i.e., Lactobacillus kefir, Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum). Nanoparticle tracking analysis showed that the size of isolated kefir-derived Lactobacillus EV was within 80 to 400 nm, and kefir-derived Lactobacillus EV uptake into recipient Caco-2 cells was confirmed by fluorescence labeling. Treatment of each kefir-derived Lactobacillus EV onto TNF-alpha-stimulated Caco-2 cells significantly reduced the level of both mRNA expression and secretion of IL-8, and Western blot analysis revealed that such an effect was related to inhibition of TNF-alpha signaling mediated by reducing the phosphorylation of p65, a subunit of NF-kB. Subsequent administration of kefir-derived Lactobacillus EV into inflammatory bowel disease-induced mice significantly alleviated the body weight loss and rectal bleeding, and enhanced stool consistency. Histological examination showed that kefir-derived Lactobacillus EV substantially reduced the infiltration of transmural leukocytes and loss of goblet cells within the colon, and the serum level of myeloperoxidase was significantly lower in the EV-treated group than control group. Our study demonstrates that kefir-derived Lactobacillus EV can be potentially used for developing innovative strategies for alleviating inflammatory bowel disease.

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