A DiR loaded tumor targeting theranostic cisplatin-icodextrin prodrug nanoparticle for imaging guided chemo-photothermal cancer therapy.

Imaging-guided diagnosis and chemo-photothermal combination therapy have promising applications for the treatment of cancer. Nevertheless, the accurate diagnosis and efficient treatment of tumors are not yet satisfactory. Herein, a tumor targeting DiR loaded cisplatin-icodextrin prodrug nanoparticle, with selective drug release, was fabricated as a multifunctional theranostic nanoplatform for chemo-photothermal combination therapy. By loading DiR into the hydrophobic domain of folic acid-icodextrin-polycaprolactone (FA-ICO-PCL, FIP) and cisplatin-icodextrin-polycaprolactone (Pt-ICO-PCL, PtIP) co-assembly, the resultant DiR@(PtIP + FIP) (DPtFIP) NPs had a diameter of around 70 nm and showed excellent tumor targeting ability and negligible side effects. Moreover, the DPtFIP NPs achieved real-time NIR fluorescence imaging of solid tumors with high contrast. By the accurate tumor imaging, local laser irradiation dramatically enhanced the chemotherapy for triple-negative breast cancer. Such a biocompatible nanotherapeutic holds great potential for tumor diagnosis and imaging-guided combinational cancer therapy.

Icodextrin Is Associated with a Lower Mortality Rate in Peritoneal Dialysis Patients.

Background:Icodextrin (ICO) improves fluid removal in peritoneal dialysis (PD) patients. However, whether physiological benefits of ICO translate into patient survival remains unclear. We examine the association of ICO and clinical outcomes.Methods:We identified patients who initiated long-term PD from the National Health Insurance Research Database of Taiwan. We matched ICO users with non-users according to propensity score and survival status when ICO was prescribed. We utilized time-dependent analyses to avoid immortal time bias. Additional competing risk models were utilized for the outcomes except for death. The outcomes of interest were time to death, technique failure, peritonitis, major adverse cardiovascular events (MACE), and hospitalization.Results:A total of 4,914 PD patients were enrolled and 2,836 PD patients (57.7%) were identified as ICO users. The ICO users had significantly better overall survival (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.63 - 0.86), especially among early ICO users (HR 0.64; 95% CI 0.54 - 0.77, p value for interaction: 0.007). The ICO users were associated with higher risk of peritonitis (subdistribution HR 1.22, 95% CI 1.06 - 1.14) and hospitalization (subdistribution HR 1.14, 95% CI 1.05 - 1.24), considering competing risk of death. However, when considering ICO use as a time-varying covariate, ICO users shared similar risks for technique failure, peritonitis, MACE, and hospitalization as non-users. The effect of ICO on mortality was especially prominent among those early users.Conclusions:After adjustments for immortal time biases, ICO users were significantly associated with approximately 20% reduction in mortality, especially among early users.

Routine Monitoring of Sodium and Phosphorus Removal in Peritoneal Dialysis (PD) Patients Treated with Continuous Ambulatory PD (CAPD), Automated PD (APD) or Combined CAPD+APD.

BACKGROUND: Adequate removal of sodium (Na) and phosphorus (P) is of paramount importance for patients with dialysis-dependent kidney disease can easily quantified in peritoneal dialysis (PD) patients. Some studies suggest that automated PD (APD) results in lower Na and P removal. METHODS: In this study we retrospectively analysed our data on Na and P removal in PD patients after implementation of a routine monitoring in 2011. Patients were stratified in those treated with continuous ambulatory PD (CAPD, n=24), automated PD (APD, n=23) and APD with one bag change (CAPD+APD, n=10). Until 2015 we collected time-varying data on Na and P removal from each patient (median 5 [interquartile range 4-8] values). RESULTS: Peritoneal Na and P removal (mmol per 24h ± standard deviation) was 102 ± 48 and 8 ± 2 in the CAPD, 90 ± 46 and 9 ± 3 in the APD and 126 ± 39 and 13 ± 2 in the CAPD+APD group (ANOVA P=0.141 and <0.001). Taking renal excretion into account total Na and P removal (mmol per 24h) was 221 ± 65 and 16 ± 5 in the CAPD, 189 ± 58 and 17 ± 6 in the APD and 183 ± 38 and 16 ± 6 in the CAPD+APD group (P=0.107 and 0.764). Over time, peritoneal removal of Na but not that of P increased in all groups. In patients with modifications of PD treatment, Na but not P removal was significantly increased over-time. CONCLUSIONS: Overall Na and P removal were similar with different PD modalities. Individualized adjustments of PD prescription including icodextrin use or higher glucose concentration can improve Na removal while P removal is mainly determined by the dialysate volume.

Knowledge and utilization of the 10 DOH-Endorsed herbal medicinal plants among resident physician trainees of the University of Santo Tomas Hospital

BACKGROUND: In the recent years, there appeared to be a rise of herbal products in the market. Thus, it becomes imperative for health practitioners to become knowledgeable on this aspect of complementary medicine. However, data on familiarity with and actual utilization of the 10 DOH-endorsed herbal medicine plants by the health practitioners is lacking.OBJECTIVE: This study was done in order to determine the knowledge and utilization of the 10 DOH-endorsed herbal medicinal plants among the resident physician trainees of the University of Santo Tomas Hospital (USTH).METHODS: A total of 143 randomly selected trainees from different specialties and year levels were included in this study. A one-time interaction with the residents was done, during which, they were asked to answer a 5-page face to face survey questionnaire.RESULTS: The study revealed that majority of the respondents is aware of the 10-DOH endorsed herbal medicinal plants. However, most of them perceive the use of herbal medicines to be only " a little effective". Prescribers are prompted mainly by its affordability. The residents can fairly identify the herbal medicinal plants and are adept with the indication for use of these plants. In spite of this, majority of the residents are not familiar with the proper preparation methods.CONCLUSION: Overall, the respondents appear to be more aware with certain herbal medicinal plants such as ampalaya, bawang, lagundi and sambong but obviously lack familiarity with other plants including ulasimang bato, yerba buena and niyog-niyogan.

Knowledge and utilization of the 10 DOH-Endorsed herbal medicinal plants among resident physician trainees of the University of Santo Tomas Hospital

@#<p style="text-align: justify;"><strong>BACKGROUND:</strong> In the recent years, there appeared to be a rise of herbal products in the market. Thus, it becomes imperative for health practitioners to become knowledgeable on this aspect of complementary medicine. However, data on familiarity with and actual utilization of the 10 DOH-endorsed herbal medicine plants by the health practitioners is lacking.<br /><strong>OBJECTIVE:</strong> This study was done in order to determine the knowledge and utilization of the 10 DOH-endorsed herbal medicinal plants among the resident physician trainees of the University of Santo Tomas Hospital (USTH).<br /><strong>METHODS:</strong> A total of 143 randomly selected trainees from different specialties and year levels were included in this study. A one-time interaction with the residents was done, during which, they were asked to answer a 5-page face to face survey questionnaire.<br /><strong>RESULTS:</strong> The study revealed that majority of the respondents is aware of the 10-DOH endorsed herbal medicinal plants. However, most of them perceive the use of herbal medicines to be only " a little effective". Prescribers are prompted mainly by its affordability. The residents can fairly identify the herbal medicinal plants and are adept with the indication for use of these plants. In spite of this, majority of the residents are not familiar with the proper preparation methods.<br /><strong>CONCLUSION:</strong> Overall, the respondents appear to be more aware with certain herbal medicinal plants such as ampalaya, bawang, lagundi and sambong but obviously lack familiarity with other plants including ulasimang bato, yerba buena and niyog-niyogan.</p>

Automated peritoneal dialysis prescriptions for enhancing sodium and fluid removal: a predictive analysis of optimized, patient-specific dwell times for the day period.

BACKGROUND: Remaining edema-free is a challenge for many automated peritoneal dialysis (APD) patients, especially those with fast ("high") transport characteristics. Although increased use of peritoneal dialysis (PD) solutions with high glucose concentrations may improve volume control, frequent use of such solutions is undesirable. METHODS: We used the 3-pore kinetic model to evaluate 4 alternative therapy prescriptions for the APD day exchange in anuric patients with high, high-average, and low-average transport characteristics. Four prescriptions were modeled: Therapy 1: Optimal, individualized dwell times with a dry period. Therapy 2: Use of a midday exchange. Therapy 3: Use of an icodextrin-containing dialysate during a 14-hour dwell. Therapy 4: Use of optimal, individualized dwell times, followed by an icodextrin dwell to complete the daytime period. The alternative therapies were compared with a reference standard therapy using glucose solution during a 14-hour dwell. The nighttime prescription was identical in all cases (10 L over 10 hours), and all glucose solutions contained 2.27% glucose. Net ultrafiltration (UF), sodium removal (NaR), total carbohydrate (CHO) absorption, and weekly urea Kt/V for a 24-hour period were computed and compared. RESULTS: The UF and NaR were substantially higher with therapy 1 than with standard therapy (1034 mL vs 621 mL and 96 mmol vs 51 mmol respectively), without significant changes in CHO absorption or urea Kt/V. However, therapy 1 resulted in reduced ß2-microglobulin clearance (0.74 mL/min vs 0.89 mL/min with standard therapy). Compared with therapy 1, therapy 2 improved UF and NaR (1062 mL vs 1034 mL and 99 mmol vs 96 mmol); however, that improvement is likely not clinically significant. Therapy 2 also resulted in a higher Kt/V (2.07 vs 1.72), but at the expense of higher glucose absorption (difference: 42 g). The UF and NaR were highest with a long icodextrin-containing daytime dwell either preceded by a short optimized dwell (1426 mL and 155 mmol) or without such a dwell (1327 mL and 148 mmol). CONCLUSIONS: The 3-pore model predictions revealed that patient-specific optimal dwell times and regimens with a longer day dwell might provide improved UF and NaR options in APD patients with a variety of peritoneal membrane transport characteristics. In patients without access to icodextrin, therapy 1 might enhance UF and NaR and provide a short-term option to increase fluid removal. Although that approach may offer clinicians a therapeutic option for the overhydrated patient who requires increased UF in the short term, APD prescriptions including icodextrin provide a means to augment sodium and fluid removal. Data from clinical trials are needed to confirm the predictions from this study.

Adhesion-preventing properties of 4% icodextrin and canola oil: a comparative experimental study.

OBJECTIVE: Postsurgical abdominal adhesions are common, serious postoperative complications. The present study compared the usefulness of 4% icodextrin and canola oil in preventing postoperative peritoneal adhesions. METHODS: Twenty-four Wistar albino rats were divided into three groups. Following a laparotomy, a serosal abrasion was made by brushing the cecum, and 3 mL of 0.9% NaCl, 4% icodextrin, or 3 mL of canola oil were intraperitoneally administered for the control, icodextrin, and canola oil groups, respectively. The abdomen was then closed. All of the rats were sacrificed at day 10. Macroscopic, histopathological, and biochemical evaluations were performed. The results were statistically analyzed using Kruskal-Wallis and ANOVA tests. RESULTS: Macroscopic analyses revealed that both canola oil and 4% icodextrin reduced adhesion formation, but the difference was not statistically significant (p = 0.17). The histopathological examinations revealed no significant differences in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM1, or PECAM1 scores. However, both canola oil and 4% icodextrin significantly reduced fibrosis (p = 0.025). In the canola oil group, the histiocytic reactions were significantly increased (p = 0.001), and the hydroxyproline levels were significantly lower than those in the other groups (p = 0.034). CONCLUSIONS: In the present study, canola oil was determined to be superior to 4% icodextrin in lowering hydroxyproline levels and increasing histiocytic reactions. Considering these results, we believe that canola oil is a promising agent for preventing adhesion formation.

Interference of maltose, icodextrin, galactose, or xylose with some blood glucose monitoring systems.

Maltose, a disaccharide composed of two glucose molecules, is used in a number of biological preparations as a stabilizing agent or osmolality regulator. Icodextrin, which is converted to maltose, is present in a peritoneal dialysis solution. Galactose and xylose are found in some foods, herbs, and dietary supplements; they are also used in diagnostic tests. When some blood glucose monitoring systems are used--specifically, those that use test strips containing the enzymes glucose dehydrogenase-pyrroloquinolinequinone or glucose dye oxidoreductase--in patients receiving maltose, icodextrin, galactose, or xylose, interference of blood glucose levels can occur. Maltose, icodextrin, galactose, and xylose are misinterpreted as glucose, which can result in erroneously elevated serum glucose levels. This interference can result in the administration of insulin, which may lead to hypoglycemia. In severe cases of hypoglycemia, deaths have occurred. If patients are receiving maltose, icodextrin, galactose, or xylose, clinicians must review the package inserts of all test strips to determine the type of glucose monitoring system being used and to use only those systems whose tests strips contain glucose oxidase, glucose dehydrogenase-nicotinamide adenine dinucleotide, or glucose dehydrogenase-flavin adenine dinucleotide.

Nutritional effects of increasing dialysis dose by adding an icodextrin daytime dwell to Nocturnal Intermittent Peritoneal Dialysis (NIPD) in children.

BACKGROUND: To assess the need to adapt dietary prescriptions, we studied potential effects of increasing the dialysis dose by adding a daytime icodextrin dwell, in children on Nocturnal Intermittent Peritoneal Dialysis (NIPD), on peritoneal amino acids (AA) and albumin loss, AA, albumin, cholesterol and fibrinogen plasma levels and nutritional intake. METHODS: A cross-over study in eight children (age 2-12 years) on NIPD at baseline (week 1). INTERVENTION: to increase dialysis dose we added a daytime dwell with 1100 ml/m(2) icodextrin solution for a week (week 2). MAIN OUTCOME MEASURES: peritoneal albumin loss (quantified by nephelometry) and AA loss (quantified by liquid chromatography mass spectrometry) in the last 72 h dialysate collections of weeks 1 and 2. On days 7 and 14, morning blood sample was taken for urea, creatinine, plasma AA levels, serum albumin, cholesterol and fibrinogen determination. Nutritional intake diaries were kept throughout the study period. RESULTS: Weekly dialysis creatinine clearance increased from 35 to 65 l/1.73 m(2) (P<0.0001) and Kt/V from 1.99 to 2.54 (P<0.01). Peritoneal albumin loss did not change significantly (2.4+/-0.4 to 2.4+/-0.3 g/m(2)/24 h) nor did serum albumin (3.25+/-0.52 to 3.21+/-0.25 g/dl), cholesterol (216+/-73 to 240+/-61 mg/dl) and fibrinogen (385+/-40 to 436+/-64 mg/dl). There was a significant increase in loss of essential (EAA) [1122+/-200 to 2104+/-417 mg/m(2)/week (P<0.0001)] and non-essential amino acids (NEAA) [6160+/-1341 to 10406+/-2899 mg/m(2)/week (P<0.001)]. Plasma AA levels did not change significantly except for a drop in histidine and glutamine. Dietary protein intake did not change from 43+/-12 to 41+/-8 g/m(2)/day, caloric intake from 73+/-21 to 70+/-24 kcal/kg/day. CONCLUSIONS: Increasing dialysis dose by introducing a daytime icodextrin dwell during a week does not affect peritoneal albumin loss, serum albumin, cholesterol and fibrinogen levels nor dietary intake on a short term. There is a significant increase in EAA and NEAA loss without change in plasma levels. We suggest monitoring dietary intake when adding a daytime icodextrin dwell in children.

A pilot study of adjuvant intraperitoneal 5-fluorouracil using 4% icodextrin as a novel carrier solution.

AIM: This pilot study utilised the sustained intraperitoneal (i.p.) dwell properties of an iso-osmotic solution of 4% icodextrin to investigate the tolerability, toxicity and feasibility of home-based i.p. 5FU adjuvant chemotherapy following resective surgery for colorectal cancer. METHODS: Twenty eligible patients (Dukes' stage B and C with potentially curative resection) underwent perioperative Tenckhoff catheter placement. Ten (6 male, 4 female, aged 46-85; mean 67.5 years) received 5FU chemotherapy. After initial flushing and gradual increase in volumes of 4% icodextrin alone, patients received home-based i.p. 5FU (150-300 mg/m(2)/day given as equal doses at 12-hourly intervals) for 14 days, with a 14-day recovery period, for a maximum of 6 courses. Two incurable patients, treated on compassionate grounds, provided further safety data. RESULTS: Nine of the 10 patients became proficient in self-treatment with 5FU and two completed 6 courses. Frequent abdominal pain was the main dose-limiting toxicity of 5FU, causing withdrawal of three patients after a high (300 mg/m(2)/day) first course and one following a third course at lower doses. I.p. 5FU concentrations (mean>30000 ngml(-1)) were 1000 fold higher than systemic venous levels. Bacterial peritonitis led to two withdrawals but was not a frequent event (microbiologically confirmed incidence of 1 per 27 catheter-months). CONCLUSIONS: Home-based i.p. adjuvant chemotherapy is a feasible treatment option in patients with surgically resected colorectal carcinoma.

New solutions for peritoneal dialysis in adult and pediatric patients.

The standard PD solutions used today contain physiological electrolyte profiles similar to that of interstitial fluids and are supplemented with glucose as the osmotic agent. Improvements in solution composition during the last 20 years have been largely restricted to minor changes in buffer and electrolyte levels. Newer PD solutions, on the other hand, are designed to manage comorbidities associated with patients on maintenance dialysis, to tailor the ultrafiltration profile based upon dwell time, and to better preserve peritoneal membrane function and host defenses. The evidence to date indicates that, in malnourished PD patients (children and adults), IP amino acids improve protein nutritional status, particularly if low protein intakes are a cause of the malnutrition. The availability of glucose polymers allows the clinician to complement standard glucose-based formulations with one that can provide improved ultrafiltration in both CAPD and APD patients for long dwells, and in patients experiencing ultrafiltration loss owing to a large effective peritoneal surface area. Owing to the reduced calorie and carbohydrate load, glucose polymers may also offer long-term metabolic advantages. Although the control of acid-base balance can be well managed in the vast majority of patients with a 35-40 mmol/L lactate solution, the development and clinical evaluation of bicarbonate-based solutions is underway as a result of concern over the potentially bioincompatible nature of acidic lactate formulations. To date, in vitro, ex vivo, and limited clinical studies show that such formulations, and in particular bicarbonate/lactate combinations are efficacious and well tolerated, and show improved peritoneal cell function versus conventional solutions. In conclusion, ongoing research and development has produced a new generation of PD solutions that, to various degrees, meet different criteria established for an ideal PD solution for chronic adult and pediatric patients on PD. These criteria include good clearance and ultrafiltration, supply of nutrition, iso-osmolality, physiologic pH, bicarbonate buffer, and minimal absorption of the osmotic agent. Several of the new solutions have already demonstrated clinical utility in controlled clinical trials and are commercially available in Europe. Wider clinical use will further add to our understanding of the impact of these formulations on patient outcomes.