Equilibrium dialysis with HPLC detection to measure substrate binding affinity of a non-heme iron halogenase.

Determination of substrate binding affinity (Kd) is critical to understanding enzyme function. An extensive number of methods have been developed and employed to study ligand/substrate binding, but the best approach depends greatly on the substrate and the enzyme in question. Below we describe how to measure the Kd of BesD, a non-heme iron halogenase, for its native substrate lysine using equilibrium dialysis coupled with High Performance Liquid Chromatography (HPLC) for subsequent detection. This method can be performed in anaerobic glove bag settings. It requires readily available HPLC instrumentation for ligand quantitation and is adaptable to meet the needs of a variety of substrate affinity measurements.

Self-perception of oral health among tertiary-care users: quanti-qualitative analysis with chronic kidney disease patients

Chronic kidney disease (CKD) has become a global public health challenge. The objective of this study was to analyze the relationship between self-perception of oral health and clinical condition among patients with CKD. This isa quanti-qualitative survey conducted in a CKD specialized service. The sample consisted of 60 patients who underwent oral examinations to have their severity of caries (DMFT) and need for dental prosthesis checked. Age, sex, time on dialysis, marital status, skin color, education and pre-existing diseases were also analyzed. Among the kidney patients who agreed to undergo the clinical examinations and showed communication skills, some were selected, and three focus groups were created, with the participation of a moderator and six to 10 kidney patients in each group. Their speeches were processed in the IRAMUTEQ software and analyzed through the similarity analysis and word cloud techniques. As for profile, the patients were aged 60.23 ± 10.87 years old; were male (73.33%); were on dialysis for 41.90 ± 56.57 months; were married (61.67%); were white (76.67%); had incomplete primary education (41.66%); had arterial hypertension (76.67%); had a DMFT index of 22.55 ± 8.39; 43.33% needed an upper complete denture; and 30.00% needed a lower complete denture. The similarity analysis revealed many doubts and uncertainties about current health services, which can be proven by the words 'no' and 'treatment'. The quanti-qualitative analysis showed a high rate of dental loss and the need for complete dentures and suggests inequities in oral health care for chronic kidney disease patients, especially in tertiary care. There was a positive representation regarding oral health, but the lexicographical analyses of the textual corpusconfirmed the self-perception of lack of dental care.

Prophylactic dialysis improves short-term clinical outcome in patients with non-dialysis-dependent chronic kidney disease undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Several studies have reported that prophylactic dialysis can reduce the mortality of non-dialysis-dependent chronic kidney disease (CKD) patients after cardiac surgery. However, the results of complications in these randomized controlled trials (RCTs) were not consistent. We aimed to perform a meta-analysis to systematically evaluate the effect of prophylactic dialysis in these non-dialysis-dependent CKD patients. METHODS: We systematically searched Medline, Embase, Cochrane's Library and other online sources for related RCTs. Effects of prophylactic dialysis on the incidence of 30 days' mortality and postoperative complications were analyzed. RESULTS: Four RCTs comprising 395 patients were included, all of them treated by coronary artery bypass grafting. Treatment of preoperative and intraoperative prophylactic dialysis significantly reduced the rate of 30-day all-cause mortality (risk ratio [RR]: 0.27, 95% confidence interval [CI], 0.13-0.58, P < 0.001, I2 = 0%) and the incidence of pulmonary complications (RR: 0.39, 95% CI, 0.20-0.77, P = 0.007, I2 = 0%), low cardiac output (RR: 0.29, 95% CI, 0.09-0.99, P = 0.05, I2 = 0%), and acute kidney injury (RR: 0.19, 95% CI: 0.07-0.52, P = 0.001, I2 = 0%). However, there were no statistically significant differences between the dialysis group and the control group in gastrointestinal bleeding, sepsis or multiple organ failure, wound infection, arrhythmia, transient neurologic deficit, stroke and re-exploration for bleeding. CONCLUSION: Prophylactic dialysis can improve the 30-day clinical outcomes of non-dialysis-dependent CKD patients undergoing cardiac surgery, it was associated with the 30-day mortality benefit and led to a decrease in the incidence of pulmonary complications, as well as low cardiac output, and acute kidney injury.

The Concentration of Organic Acids in Cranberry Juice Modulates the Gut Microbiota in Mice.

A daily consumption of cranberry juice (CJ) is linked to many beneficial health effects due to its richness in polyphenols but could also awake some intestinal discomforts due to its organic acid content and possibly lead to intestinal inflammation. Additionally, the impact of such a juice on the gut microbiota is still unknown. Thus, this study aimed to determine the impacts of a daily consumption of CJ and its successive deacidification on the intestinal inflammation and on the gut microbiota in mice. Four deacidified CJs (DCJs) (deacidification rates of 0, 40, 60, and 80%) were produced by electrodialysis with bipolar membrane (EDBM) and administered to C57BL/6J mice for four weeks, while the diet (CHOW) and the water were ad libitum. Different parameters were measured to determine intestinal inflammation when the gut microbiota was profiled. Treatment with a 0% DCJ did not induce intestinal inflammation but increased the gut microbiota diversity and induced a modulation of its functions in comparison with control (water). The effect of the removal of the organic acid content of CJ on the decrease of intestinal inflammation could not be observed. However, deacidification by EDBM of CJ induced an additional increase, in comparison with a 0% DCJ, in the Lachnospiraceae family which have beneficial effects and functions associated with protection of the intestine: the lower the organic acid content, the more bacteria of the Lachnospiraceae family and functions having a positive impact on the gut microbiota.

A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients. METHODS: A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded. RESULTS: Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011]. CONCLUSION: In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.

Comparison of free thyroxine measurement by chemiluminescence and equilibrium dialysis following 131I therapy in hyperthyroid cats.

OBJECTIVES: The first objective was to assess correlation between free thyroxine (fT4) measurements by equilibrium dialysis (fT4ED; Antech Diagnostics) and a chemiluminescent enzyme immunoassay (fT4CEIA; IMMULITE 2000 Veterinary Free T4 [Siemens Healthcare Diagnostics Products]) in hyperthyroid, otherwise healthy, cats before (T0), and 1 month (T1) and 11-23 months (T2) after radioactive iodine (131I) therapy. The second objective was to determine correlation between thyroid status based on fT4 (by both techniques) and the gold standard, thyroid scintigraphy. METHODS: Thyroid status, including thyroid-stimulating hormone (TSH), total thyroxine (TT4) and fT4 serum concentrations, were assessed in 45 client-owned hyperthyroid cats before (T0), and 1 month (T1) and 11-23 months (T2) after 131I therapy. fT4 was determined by a chemiluminescent enzyme immunoassay (CEIA) and equilibrium dialysis (ED). Quantitative thyroid scintigraphy (with sodium 99m-Tc-pertechnetate) was performed at T2. RESULTS: Spearman correlation between fT4CEIA and fT4ED was 0.81, 0.88 and 0.79 at T0, T1 and T2, respectively. fT4CEIA was consistently lower than fT4ED, with a median difference of -5.4 pmol/l (P <0.001) and -4.9 pmol/l (P <0.0001) at T1 and T2, respectively. At T2, all cats were identified as euthyroid based on thyroid scintigraphy. None of the cats were identified as being hypothyroid, based on serum TT4 and TSH measurements. Nine of 22 (40.9%) cats had an fT4CEIA below the reference interval (RI) at T2, whereas only 2/22 (9.1%) cats had an fT4ED concentration below the RI at T2. CONCLUSIONS AND RELEVANCE: Good correlation exists between both assays at T1 and T2, but a significant systematic difference is noted at both time points. This could be an indication for reconsideration of the current RI, although further studies are warranted for assessing test accuracy (in otherwise healthy cats and cats with non-thyroidal illness). At this time, routine use of fT4CEIA after 131I therapy is not advised in feline patients.

Evaluation of the feasibility of short-term electrodialysis for separating naturally occurring fluoride from instant brick tea infusion.

BACKGROUND: Removing excessive naturally occurring fluoride from tea and/or infusions is difficult because the process has low efficiency and causes secondary pollution. In this study, a novel electrodialysis (ED) technology was developed. We examined the effect of crucial parameters (electrolyte concentration, operation voltage, ED duration and initial concentration of the tea infusion) on defluoridation performance using a highly efficient ion-exchange membrane with five-compartment cells. RESULTS: The most effective ED system results were obtained at an electrolyte concentration of 10 g kg-1 and operating voltage of 20 V. Moreover, the fluoride removal capacity (10.70-66.93%) was highly dependent on the ED duration (1-15 min) and initial concentration of the tea infusion (0.5-10 g kg-1 ). The longer the ED duration and the lower the initial concentration, the higher was the defluoridation performance. During ED, limited loss of the main inclusions (total polyphenols, catechins, caffeine and selected ions) was observed. Furthermore, the D201 anion resin-filled ED stack (0.5-5 g) and improvement of concentrate compartment electrolyte (≥5 times the dilute compartment electrolyte) in the ED system enhanced the defluoridation rate significantly. CONCLUSION: ED is a potentially effective method that can be used for defluoridation in the deep processing of tea products. © 2019 Society of Chemical Industry.

Awareness, Understanding and Treatment Practices when Managing Cachexia in End-Stage Kidney Disease.

BACKGROUND: Cachexia is a wasting syndrome found within a range of chronic illnesses/life-limiting conditions, however awareness and understanding of cachexia amongst renal Health Care Professionals has not been investigated. OBJECTIVES: To ascertain the awareness, understanding and treatment practices of Health Care Professionals who provide care for people with cachexia and end-stage renal disease. METHODS: Health Care Professionals were recruited via the European Dialysis and Transplant Nurses Association/European Renal Care Association in September 2018. This was an exploratory study using a mixed-methods approach with those who provide care for patients with end-stage renal disease and cachexia. An online survey and two focus groups were conducted. Descriptive statistics and inductive thematic analysis were used to explore current knowledge and practices in renal cachexia. RESULTS: A total of 93 participants from 30 countries completed the online survey. Twelve Health Care Professionals agreed to participate in the focus groups. Reduced appetite, weight loss and muscle loss in relation to cachexia were accurately described, but the percentage of weight loss was unknown. The importance of multi-professional collaboration was recognised, however, the current management of cachexia was wide-ranging. Quality of life, patient-clinician communication and specialist support for carers were regarded as vital. CONCLUSION: Timely identification and management of cachexia are needed to improve the quality of life for patients and appropriately support families. In order for these goals to be achieved, there is a need to increase awareness and understanding of cachexia amongst renal nurses.

Extraction, formulation and characterization of an in vitro and ex-vivo evaluation of Thymus serpyllum L. (Thymus oil) from topical preparations using dialysis cellulose membrane and natural rabbit skin.

Herbal remedies like the Thymus serpyllum L. is useful in traditional medicine for the treatment of many diseases especially congestion, and bronchitis. The purpose of this study was to formulate a micro-emulsion, a gel and an ointment containing the plant hydro distilled thymus oil extracted from Thymus serpyllum L. collected from Ziarat, Balochistan. The prepared formulations were subjected to in-vitro and ex vivo study release, High performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC), to justify their suitability for topical use. The in-vitro and ex-Vivo release was studied using Franz Cells and using two different kinds of membrane synthetic dialysis cellulose membrane and natural rabbit skin and the amount of drug released was determined by HPLC at λ 274nm. The three formulations result obtained through dialysis cellulose membrane showed the faster release than the natural rabbit skin. However, the micro-emulsion, gel formulation showed the same release except ointment. The release from the above mentioned formulation can be arranged in the following descending order. micro-emulsion > Gel > Ointment. The best fit of release kinetics was achieved by Krosmeyer- Peppas, the TLC and HPLC identifies the Thymol, isolation and quantification of the marker. This study demonstrates that it is necessary to assess the impact of release and permeability pattern of different formulations. In vitro and ex-vivo diffusion cell experiments can be utilized to develop formulations of traditional medicines identifies.

Effect of C-terminal His-tag and purification routine on the activity and structure of the metalloenzyme, l-alanyl-d-glutamate peptidase of the bacteriophage T5.

In this work, we studied the effect of the C-terminally attached poly-histidine tag (His-tag), as well as the peculiarities of the protein purification procedure by the immobilized metal affinity chromatography (IMAC) on the activity and structure of the metalloenzyme, l-alanyl-d-glutamate peptidase of bacteriophage T5 (EndoT5), whose zinc binding site and catalytic aspartate are located near the C-terminus. By itself, His-tag did not have a significant effect on either activity or folding of the polypeptide chain, nor on the binding of zinc and calcium ions to the protein. However, the His-tagged EndoT5 samples had low shelf-life, with storage of these samples resulting in an increased propensity for protein self-association and decreased enzymatic activity of EndoT5. Furthermore, disastrous effects on the activity of the enzyme were exerted by the presence of imidazole and nickel ions accompanying metal chelate chromatography. The activity of the protein can be restored by thorough washing off of these low molecular impurities via the prolonged dialysis of the His-tagged EndoT5 samples at the specifically elaborated conditions.

Incidents related to the Hickman® catheter: identification of damages.

OBJECTIVE: to identify damages resulting from incidents with the Hickman® catheter. METHOD: descriptive, retrospective, qualitative approach. The source of data were the notifications of incidents that occurred between January 2012 and May 2015, as well as the information available on the medical records of patients involved in incidents with the Hickman® catheter. RESULTS: the incidents related to the Hickman® catheter with the greatest impact on patient care were obstruction, fracture and traction. All incidents caused damage to patients, in a greater or lesser degree, in the dimensions of physical damage and subjective damage. FINAL CONSIDERATIONS: damage or potential risk of damage was present in all incidents analyzed. The need to revise cleaning and obstruction protocols for the maintenance of the permeability of Hickman® catheters was demonstrated.

Incidents related to the Hickman® catheter: identification of damages / Incidentes relacionados con el catéter de Hickman®: identificación del daño / Incidentes relacionados ao cateter de Hickman®: identificação de dano

ABSTRACT Objective: to identify damages resulting from incidents with the Hickman® catheter. Method: descriptive, retrospective, qualitative approach. The source of data were the notifications of incidents that occurred between January 2012 and May 2015, as well as the information available on the medical records of patients involved in incidents with the Hickman® catheter. Results: the incidents related to the Hickman® catheter with the greatest impact on patient care were obstruction, fracture and traction. All incidents caused damage to patients, in a greater or lesser degree, in the dimensions of physical damage and subjective damage. Final considerations: damage or potential risk of damage was present in all incidents analyzed. The need to revise cleaning and obstruction protocols for the maintenance of the permeability of Hickman® catheters was demonstrated.

RESUMEN Objetivo: identificar el acaecimiento de daños en incidentes relacionados con el catéter de Hickman®. Método: investigación descriptiva, retrospectiva, de abordaje cualitativo. Como fuente de datos, se utilizaron fichas de notificación de incidentes ocurridos entre enero de 2012 y mayo de 2015, además de informaciones relatadas en los prontuarios de los pacientes involucrados en los incidentes relacionados con el catéter de Hickman®. Resultados: los incidentes de impacto más importantes en la atención al paciente, relacionados con el catéter de Hickman®, fueron la obstrucción, la fractura y la tracción. Todos los incidentes generaron, en mayor o menor grado, daños a los pacientes en las dimensiones física y subjetiva. Consideraciones finales: se encontraba presente en todos los incidentes analizados, el daño en sí mismo o el riesgo potencial para el daño. Quedó en evidencia la necesidad de revisar los protocolos de lavado y bloqueo del catéter de Hickman® para el mantenimiento de su permeabilidad.

RESUMO Objetivo: identificar a ocorrência de danos nos incidentes relacionados ao cateter de Hickman®. Método: pesquisa descritiva, retrospectiva, de abordagem qualitativa. Como fonte dos dados, foram utilizadas as fichas de notificação de incidentes ocorridos entre janeiro de 2012 e maio de 2015, além de informações dos prontuários dos pacientes envolvidos com incidentes relacionados ao cateter de Hickman®. Resultados: os incidentes, relacionados ao cateter de Hickman®, de maior impacto para a assistência ao paciente foram a obstrução, fratura e tração. Todos os incidentes geraram dano aos pacientes, de maior ou menor grau, nas dimensões de dano físico e danos subjetivos. Considerações finais: dano ou risco potencial para dano esteve presente em todos os incidentes analisados. Evidenciou-se a necessidade de revisar os protocolos de lavagem e bloqueio para a manutenção da permeabilidade do cateter de Hickman®.

Smart polymeric nanoparticles with pH-responsive and PEG-detachable properties for co-delivering paclitaxel and survivin siRNA to enhance antitumor outcomes.

BACKGROUND: The co-delivery of chemotherapeutic agents and small interfering RNA (siRNA) within one cargo can enhance the anticancer outcomes through its synergistic therapeutic effects. MATERIALS AND METHODS: We prepared smart polymeric nanoparticles (NPs) with pH-responsive and poly(ethylene glycol) (PEG)-detachable properties to systemically co-deliver paclitaxel (PTX) and siRNA against survivin gene for lung cancer therapy. The cationic polyethyleneimine-block-polylactic acid (PEI-PLA) was first synthesized and characterized, with good biocompatibility. PTX was encapsulated into the hydrophobic core of the PEI-PLA polymers by dialysis, and then the survivin siRNA was loaded onto the PTX-loaded NPs (PEI-PLA/PTX) through electrostatic interaction between siRNA and PEI block. Finally, the negatively charged poly(ethylene glycol)-block-poly(L-aspartic acid sodium salt) (PEG-PAsp) was coated onto the surface of NPs by electrostatic interaction to form final smart polymeric NPs with mean particle size of 82.4 nm and zeta potential of 4.1 mV. After uptake of NPs by tumor cells, the PEG-PAsp segments became electrically neutral owing to the lower endosome pH and consequently detached from the smart NPs. This process allowed endosomal escape of the NPs through the proton-sponge effect of the exposed PEI moiety. RESULTS: The resulting NPs achieved drug loading of 6.04 wt% and exhibited good dispersibility within 24 h in 10% fetal bovine serum (FBS). At pH 5.5, the NPs presented better drug release and cellular uptake than at pH 7.4. The NPs with survivin siRNA effectively knocked down the expression of survivin mRNA and protein owing to enhanced cell uptake of NPs. Cell counting kit-8 (CCK-8) assay showed that the NPs presented low systemic toxicity and improved antiproliferation effect of PTX on A549 cells. Moreover, in vivo studies demonstrated that accumulated NPs in the tumor site were capable of inhibiting the tumor growth and extending the survival rate of the mice by silencing the survivin gene and delivering PTX into tumor cells simultaneously. CONCLUSION: These results indicate that the prepared nano-vectors could be a promising co-delivery system for novel chemo/gene combination therapy.

Controversies in Management of Hyperkalemia.

BACKGROUND: Hyperkalemia is a common electrolyte disorder that can result in morbidity and mortality if not managed appropriately. OBJECTIVES: This review evaluates the classic treatments of hyperkalemia and discusses controversies and new medications for management. DISCUSSION: Potassium (K+) plays a key role in determining the transmembrane potentials of "excitable membranes" present in nerve and muscle cells. K+ is the predominant intracellular cation, and clinical deterioration typically ensues when patients develop sufficiently marked elevation in extracellular fluid concentrations of K+ (hyperkalemia). Hyperkalemia is usually detected via serum clinical laboratory measurement. The most severe effect of hyperkalemia includes various cardiac dysrhythmias, which may result in cardiac arrest and death. Treatment includes measures to "stabilize" cardiac membranes, to shift K+ from extracellular to intracellular stores, and to promote K+ excretion. Calcium gluconate 10% dosed 10 mL intravenously should be provided for membrane stabilization, unless the patient is in cardiac arrest, in which case 10 mL calcium chloride is warranted. Beta-agonists and intravenous insulin should be given, and some experts recommend the use of synthetic short-acting insulins rather than regular insulin. Dextrose should also be administered, as indicated by initial and serial serum glucose measurements. Dialysis is the most efficient means to enable removal of excess K+. Loop and thiazide diuretics can also be useful. Sodium polystyrene sulfonate is not efficacious. New medications to promote gastrointestinal K+ excretion, which include patiromer and sodium zirconium cyclosilicate, hold promise. CONCLUSIONS: Hyperkalemia can be deadly, and treatment requires specific measures including membrane stabilization, cellular shift, and excretion.

Multifunctional fluorescent iron quantum clusters for non-invasive radiofrequency ablationof cancer cells.

This work reports the potential of iron quantum clusters (FeQCs) as a hyperthermia agent for cancer, by testing its in-vitro response to shortwave (MHz range), radiofrequency (RF) waves non-invasively. Stable, fluorescent FeQCs of size ∼1 nm prepared by facile aqueous chemistry from endogenous protein haemoglobin were found to give a high thermal response, with a ΔT ∼50 °C at concentrationsas low as165 µg/mL. The as-prepared nanoclusters purified by lyophilization as well as dialysis showed a concentration, power and time-dependent RF response, with the lyophilized FeQCs exhibiting pronounced heating effects. FeQCs were found to be cytocompatible to NIH-3T3 fibroblast and 4T1 cancer cells treated at concentrations upto 1000 µg/mL for 24 h. Upon incubation with FeQCs and exposure to RF waves, significant cancer cell death was observed which proves its therapeutic ability. The fluorescent ability of the clusters could additionally be utilized for imaging cancer cells upon excitation at ∼450 nm. Further, to demonstrate the feasibility of imparting additional functionality such as drug/biomolecule/dye loading to FeQCs, they were self assembled with cationic polymers to form nanoparticles. Self assembly did not alter the RF heating potential of FeQCs and additionally enhanced its fluorescence. The multifunctional fluorescent FeQCs therefore show good promise as a novel therapeutic agent for RF hyperthermia and drug loading.

Lactate gap as a tool in identifying ethylene glycol poisoning.

Ethylene glycol toxicity is a known cause of anion gap metabolic acidosis, with the presence of an osmolar gap and the right clinical context suggesting to the diagnosis. Rapid recognition and early treatment is crucial. Unfortunately, ethylene glycol levels are not readily available and must be performed at a reference laboratory. We present a case where recognising the significance of the 'lactate gap' assisted in identifying ethylene glycol poisoning.

Pharmacokinetics of meropenem in septic patients on sustained low-efficiency dialysis: a population pharmacokinetic study.

BACKGROUND: The aim of the study was to describe the population pharmacokinetics (PK) of meropenem in critically ill patients receiving sustained low-efficiency dialysis (SLED). METHODS: Prospective population PK study on 19 septic patients treated with meropenem and receiving SLED for acute kidney injury. Serial blood samples for determination of meropenem concentrations were taken before, during and after SLED in up to three sessions per patient. Nonparametric population PK analysis with Monte Carlo simulations were used. Pharmacodynamic (PD) targets of 40% and 100% time above the minimal inhibitory concentration (f T > MIC) were used for probability of target attainment (PTA) and fractional target attainment (FTA) against Pseudomonas aeruginosa. RESULTS: A two-compartment linear population PK model was most appropriate with residual diuresis supported as significant covariate affecting meropenem clearance. In patients without residual diuresis the PTA for both targets (40% and 100% f T > MIC) and susceptible P. aeruginosa (MIC ≤ 2 mg/L) was > 95% for a dose of 0.5 g 8-hourly. In patients with a residual diuresis of 300 mL/d 1 g 12-hourly and 2 g 8-hourly would be required to achieve a PTA of > 95% and 93% for targets of 40% f T > MIC and 100% f T > MIC, respectively. A dose of 2 g 8-hourly would be able to achieve a FTA of 97% for 100% f T > MIC in patients with residual diuresis. CONCLUSIONS: We found a relevant PK variability for meropenem in patients on SLED, which was significantly influenced by the degree of residual diuresis. As a result dosing recommendations for meropenem in patients on SLED to achieve adequate PD targets greatly vary. Therapeutic drug monitoring may help to further optimise individual dosing. TRIAL REGISTRATION: Clincialtrials.gov, NCT02287493 .

Cancer Anorexia and Cachexia: Screening in an Ambulatory Infusion Service and Nutrition Consultation
.

BACKGROUND: Cancer anorexia-cachexia syndrome compromises physical function and nutritional and emotional well-being. Systematic screening followed by nutrition referral for appropriate interventions is rare.
. OBJECTIVES: The purpose of this study was to pilot a screening process followed by nutritional assessment and intervention when warranted for patients with lung malignancies.
. METHODS: Adult patients with lung malignancies were invited to complete the 12-item Anorexia/Cachexia Scale (A/CS-12) on the day of chemotherapy initiation in ambulatory infusion. Those who scored at a preset threshold were referred to nutrition services for a comprehensive assessment and intervention plan. Those who scored better than the threshold completed the A/CS-12 at each infusion visit for as many as 16 weeks. 
. FINDINGS: 90 participants enrolled, and 46 scored in a moderate-to-severe-risk category; of those, 42 were referred to nutrition services.