Photodynamic inactivation of <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester

The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.     

Effect of the transdermal low-level laser therapy on endothelial function

The effect of low-level laser therapy (LLLT) on the cardiovascular system is not fully established. Since the endothelium is an important endocrine element, establishing the mechanisms of LLLT action is an important issue.The aim of the study was to evaluate the effect of transdermal LLLT on endothelial function.In this study, healthy volunteers (n?=?40, age?=?20–40 years) were enrolled. N?=?30 (14 female, 16 male, mean age 30?±?5 years) constituted the laser-irradiated group (LG). The remaining 10 subjects (6 women, 4 men, mean age 28?±?5 years) constituted the control group (CG). Participants were subjected to LLLT once a day for three consecutive days. Blood for biochemical assessments was drawn before the first irradiation and 24 h after the last session. In the LG, transdermal illumination of radial artery was conducted (a semiconductor laser λ?=?808 nm, irradiation 50 mW, energy density 1.6 W/cm² and a dose 20 J/day, a total dose of 60 J). Biochemical parameters (reflecting angiogenesis: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiostatin; antioxidative status: glutathione (GSH) and the nitric oxide metabolic pathway: symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA) and l-arginine) were assessed. In the LG, a significant increase in GSH levels and considerable decrease in angiostatin concentration following the LLLT were observed. No significant differences in levels of the VEGF, FGF, SDMA, ADMA were observed.LLLT modifies vascular endothelial function by increasing its antioxidant and angiogenic potential. We found no significant differences in levels of the nitric oxide pathway metabolites within 24 h following the LLLT irradiation.     

Photodynamic inactivation of pathogenic species <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> and <Emphasis Type="Italic">Candida albicans</Emphasis> with lutetium (III) acetate phthalocyanines and specific light irradiation

Photodynamic inactivation (PDI) is a light-associated therapeutic approach suitable for treatment of local acute infections. The method is based on specific light-activated compound which by specific irradiation and in the presence of molecular oxygen produced molecular singlet oxygen and other reactive oxygen species, all toxic for pathogenic microbial cells. The study presents photodynamic impact of two recently synthesized water-soluble cationic lutetium (III) acetate phthalocyanines (LuPc-5 and LuPc-6) towards two pathogenic strains, namely, the Gram-negative bacterium Pseudomonas aeruginosa and a fungus Candida albicans. The photodynamic effect was evaluated for the cells in suspensions and organized in 48-h developed biofilms. The relatively high levels of uptakes of LuPc-5 and LuPc-6 were determined for fungal cells compared to bacterial cells. The penetration depths and distribution of both LuPcs into microbial biofilms were investigated by means of confocal fluorescence microscopy. The photoinactivation efficiency was studied for a wide concentration range (0.85–30 μM) of LuPc-5 and LuPc-6 at a light dose of 50 J cm^?2 from red light-emitting diode (LED; 665 nm). The PDI study on microbial biofilms showed incomplete photoinactivation (<3 logs) for the used gentle drug-light protocol.     

Is there a relationship between spinal instability in neoplastic disease and Tokuhashi scoring system?

Spinal instability neoplastic score (SINS) classification evaluates spinal stability by adding together six radiographic and clinical components. The objective of this study was to verify the association between SINS and Tokuhashi scoring system (TSS) score. Fifty-eight patients with vertebral metastases were admitted from 2010 to 2014 at Hospital do Servidor Público Estadual de São Paulo. They were evaluated according to their SINS and Tokuhashi SS score. Fourteen patients (24.13 %) scored from 0 to 6 points (stable spine), 37 (63.79 %) scored from 7 to 12 (potentially unstable), and 7 (12.06 %) scored from 13 to 18 (unstable). In stable spine patients according to SINS, the mean TSS score was 9.2. In potentially unstable spine patients, the mean TSS score was 8.24. In unstable spine patients, mean TSS score was 6.28. There was a statistically significant difference of the TSS score between stable and unstable patients. After evaluating TSS score in each patient, the worse the SINS, the worse was also the TSS score.     

Extracranial-intracranial bypass for internal carotid/middle cerebral atherosclerotic steno-occlusive diseases in conjunction with carotid endarterectomy for contralateral cervical carotid stenosis: clinical results and cognitive performance

Clinical results as well as cognitive performances after extracranial to intracranial (EC-IC) bypass in conjunction with contralateral carotid endarterectomy (CEA) are poorly understood. Data from 14 patients who underwent unilateral EC-IC bypass for atherosclerotic internal carotid artery (ICA)/middle cerebral artery (MCA) steno-occlusive disease in conjunction with CEA for contralateral cervical carotid stenosis were retrospectively reviewed. Postoperative results were evaluated by MRI imagings. Nine patients also underwent neuropsychological examinations (NPEs), including assessment by the Wechsler Adult Intelligence Scale-Third Edition and the Wechsler Memory Scale-Revised (WMS-R) before and about 6 months after bilateral surgeries. Postoperative MRI follow-up (median, 8 months; interquartile range, 7–8 months) confirmed successful bypass in all patients, with no additional ischemic lesions on T2WI when compared with preoperative imaging. Further, MRA showed patent bypass and contralateral smooth patency at CEA portion in all patients. In the group rate analysis, all five postoperative NPE scores (Verbal IQ, Performance IQ, WMS-memory, WMS-attention, and Average scores of all those four scores) were improved relative to preoperative NPE scores. Performance IQ and Average score improvements were statistically significant. Clinical results after EC-IC bypass in conjunction with contralateral CEA were feasible. Based on the group rate analysis, we conclude that successful unilateral EC-IC bypass and contralateral carotid endarterectomy does not adversely affect postoperative cognitive function.     

Identification of physical and psychosocial problems associated with diabetic nephropathy using the International Classification of Functioning,Disability and Health Core Set for Diabetes Mellitus

Background

We previously demonstrated validation of the Comprehensive International Classification of Functioning, Disability and Health Core Set for Diabetes Mellitus (ICF-CS for DM) in patients with diabetic nephropathy (DMN). The objective of the present study was to identify differences in experience of physical and psychosocial problems between DMN patients with and without hemodialysis (HD), and diabetes patients without nephropathy using the ICF-CS for DM.

Methods

A total of 302 diabetes outpatients (men, 68 %; mean age, 62 years) were interviewed using four components of the ICF-CS for DM including “Body functions”, “Body structures”, “Activities and participation”, and “Environmental factors”.

Results

The mean number of categories in which difficulty was experienced in the four components was significantly greater in DMN patients with HD followed by DMN patients without HD, and diabetes patients without nephropathy (23.9 vs. 18.0 vs. 13.1, respectively). Multivariate logistic regression models revealed that, compared with diabetes patients without nephropathy, diabetes patients with nephropathy were more likely to have difficulty with physical problems and social activities and participation. Among DMN patients, dialysis patients were found to have larger numbers of problems, and face difficulty with employment status after adjusting for sex, age, type, and duration of diabetes.

Conclusion

The results of this study using the ICF-CS for DM identified the areas for improvement among physical and psychosocial problems in DMN patients with and without HD in contrast to diabetes patients without nephropathy.

     

RIFLE classification in geriatric patients with acute kidney injury in the intensive care unit

Background

The RIFLE classification is widely used to assess the severity of acute kidney injury (AKI), but its application to geriatric AKI patients complicated by medical problems has not been reported.

Methods

We investigated 256 geriatric patients (≥65 years old; mean age, 74.4 ± 6.3 years) who developed AKI in the intensive care unit (ICU) according to the RIFLE classification. Etiologic, clinical, and prognostic variables were analyzed.

Results

They were categorized into RIFLE-R (n = 53), RIFLE-I (n = 102), and RIFLE-F (n = 101) groups. The overall in-hospital mortality was 39.8 %. There were no significant differences in RIFLE category between survivors and non-survivors. Survivors had significantly less needs for a ventilator and vasopressor, and lower number of failing organs. Survivors had higher systolic blood pressure, hemoglobin level, and serum albumin levels. We performed a logistic regression analysis to identify the independent predictors of in-hospital mortality. In a univariate analysis, hypertension, chronic kidney disease, RIFLE classification, number of failing organs, need for a ventilator and vasopressor, systolic blood pressure, hemoglobin level, and serum albumin levels were identified as prognostic factors of in-hospital mortality. However, in a multivariate analysis, hypertension, chronic kidney disease, number of failing organs, and serum albumin levels were independent risk factors, with no significant difference for in-hospital mortality with the RIFLE classification.

Conclusion

The RIFLE classification might not be associated with mortality in geriatric AKI patients in the ICU. In geriatric patients with AKI, various factors besides severity of AKI should be considered to predict mortality.

     

Early response to erythropoiesis-stimulating agents in non-dialysis chronic kidney disease patients

Background

Renal anemia complicated with chronic kidney disease is usually treated with erythropoiesis-stimulating agents (ESAs). However, few studies have compared the early response of hemoglobin (Hb) to different kinds of ESAs.

Methods

The effects of three types of ESAs—epoetin alfa or beta (EPO), darbepoetin alfa (DPO), and epoetin beta pegol (EPObp)—on renal anemia were followed in 416 pre-dialysis chronic kidney disease (CKD) patients. After the initial 12-week administration of ESAs, ΔHb/ESA dose/kg was calculated as an index of efficacy of each ESA. Furthermore, independent variables associated with ΔHb/ESA dose/kg (dependent variable) were determined using multiple linear regression analysis. The ten independent variables selected for analysis were: presence of diabetic nephropathy, estimated glomerular filtration rate (eGFR), Hb, albumin, iron (Fe), transferrin saturation (TSAT), ferritin, phosphate (P), intact parathyroid hormone (iPTH), and C-reactive protein.

Results

The efficacy of DPO and EPObp were similar and higher than EPO. TSAT was most strongly correlated with ΔHb/EPO dose/kg in all three types of ESAs. Other significant independent factors were Hb, albumin, P, iPTH, and diabetic nephropathy in the EPO group, eGFR in the DPO group, and Fe in the EPObp group. The adjusted coefficient of determination (R ²) ranged from 0.415 to 0.520 in the three ESA groups.

Conclusions

The study results suggest that TSAT is the best predictor of the initial 12-week responsiveness to ESA, irrespective of the type. Variables not investigated in this study also affect responsiveness to ESA in Japanese pre-dialysis CKD patients.

     

Heart rate variability is an indicator for intradialytic hypotension among chronic hemodialysis patients

Background

Intradialytic hypotension (IDH) carries adverse impact. Heart rate variability (HRV) represents autonomic cardiac regulation which influences intradialytic blood pressure. We aimed to evaluate the association between IDH and HRV.

Methods

This prospective study was carried out in a teaching hospital in Taiwan from June to August 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled and received HRV measurements for 4 times (before and during an index hemodialysis session). Patients were categorized by the changes of systolic blood pressure during the index hemodialysis into Group 1 (elevation >20 mmHg), Group 2 (decrease >20 mmHg), and Group 3 (others). Then we compared HRV indices among the three groups, and determined the indicators for IDH.

Results

One hundred and seventy-one patients (96 women, mean age 64.9 years) were enrolled and categorized into Group 1 (n = 47, 27.5 %), Group 2 (n = 45, 26.3 %) and Group 3 (n = 79, 46.2 %). Comparing with Group 1 and/or Group 3, Group 2 had significantly higher blood pressure at hemodialysis initiation (most p < 0.001) and statistically lower levels of HRV indices including variance, total power, very low-frequency, low-frequency and high-frequency since the middle phase of the hemodialysis. By logistic regression method, higher systemic blood pressure [odds ratio (OR) 1.048; p < 0.001], heart rate (OR 1.093; p = 0.021), low-frequency/high-frequency ratio (OR 1.715; p = 0.022), as well as lower variance (OR 0.639; p = 0.048) at hemodialysis initiation were independently associated with intradialytic blood pressure changes.

Conclusions

HRV is a useful indicator for IDH among hemodialysis patients.

     

Cross-cultural adaptation and validation of the International Knee Documentation Committee Subjective Knee Form in Greek

Background

Patient-reported outcomes require validation in a particular language and culture before administration for clinical use.

Materials and methods

A systematic translation of the IKDC Subjective Knee Form was initially tested in 30 patients with various knee pathologies to develop the first Greek version (IKDC/SKF-GR). It was then administered to another 80 patients. The test–retest reliability (n = 35) and internal consistency (n = 80) were examined. Construct validity was tested by correlating the IKDC/SKF-GR with the SF-36 subscales (n = 80) and content validity by measuring floor/ceiling effects. Responsiveness was measured in patients with meniscus pathology (n = 24).

Results

Patients filled the form without omissions/questions regarding the phrasing of items. Internal consistency was good (Cronbach’s α = 0.87) and test–retest reliability very good (ICC_2,1 = 0.95, SEM = 4.4 and SDC = 12.2). Correlations with the SF-36 subscales confirmed its construct validity. No floor/ceiling effects were recorded. The effect size was large (ES = 1.26).

Conclusions

The IKDC/SKF-GR has comparable measurement properties to the original form.

Level of evidence

Level II.