A Highly Translatable Dual-arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor-bearing Brain Tissues.

Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127/PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127/PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127/PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127/PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127/PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127/PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.

On the CO2 gain in on-line hemodiafiltration.

BACKGROUND: The dialysis bath holds up to 90 mmHg carbon dioxide (CO2 ) in order to keep pH low and salts in their soluble forms. CO2 crosses the dialyzer membrane and diffuses to patients. In post-dilution on-line hemodiafiltration (HDF) many liters of CO2 -containing dialysis bath - in the form of infusate - are delivered directly to patients bypassing the filtering membrane, but the precise amount of CO2 delivered is unknown. METHODS: To gain insights on this issue 18 outpatients undergoing their regular on-line HDF were investigated by means of blood gas analysis. RESULTS: Arterial pre-dialysis samples show slight hypocapnia (35.40 ± 3.22 mmHg) consistent with the secondary compensatory response to metabolic acidosis. In blood coming back to patients (venous line of extracorporeal circuit) pCO2 doubled, amounting to 69 ± 5.5 mmHg (P < .0001 with respect to pre-dialysis values) hence in on-line HDF a CO2 gain does occur. Turning off the infusate flux pump, pCO2 decreased to 63.1 ± 5.8 mmHg (P = .004) meaning that delivery of infusate in post-dilution mode significantly contributes to CO2 gain, albeit by a small amount. CONCLUSION: On-line HDF is featured by CO2 delivery to patients, in part dragged by the infusate.

Neonatal extravasation injuries: neonatal unit reflection and literature review.

Extravasation injury is tissue infiltration and injury related to drugs or infusates. Preterm infants are most susceptible due to many factors related to their prematurity. Our aim was to report on the prevalence of extravasation injury in our neonatal unit to attract attention to the existence of this problem in the neonatal units. This is an observational, longitudinal, hospital-based study, conducted in the period from February 2012 to February 2019. All preterm infants admitted to Sea Port Hospital Neonatal Unit, Port Sudan City, Sudan, were included. Infants with any other congenital or transient skin diseases were ruled out. From 434 preterm infants admitted, 249 (57.4%) infants were affected and 28 (11.2%) of them were injured significantly. We concluded that neonatal extravasation injuries (including severe forms) are significantly observed in our neonatal unit, and measures to screen for, avoid, and treat this morbidity, should be implemented.

Hyperglycemia During Home Parenteral Nutrition Administration in Patients Without Diabetes.

BACKGROUND: Parenteral nutrition (PN) is a life-sustaining therapy in appropriate clinical settings. In the hospital setting, some nondiabetic patients develop hyperglycemia and subsequently require long-term insulin while receiving PN. Whether similar hyperglycemia is seen in the outpatient setting is unclear. METHODS: We studied patients enrolled in the Mayo Clinic Home Parenteral Nutrition (HPN) program between January 1, 2010, and December 31, 2012. Patients were excluded if they had diabetes mellitus type 2 (DM2), had previously received HPN, had taken corticosteroids, or were at risk for refeeding syndrome. RESULTS: Of 144 enrolled patients, 93 met inclusion criteria with 39 patients requiring the addition of insulin to HPN. The mean age of the insulin-requiring group (IR) was higher than that of the non-insulin-requiring group (NIR) (60.74 ± 13.62 years vs 48.97 ± 17.62 years, P < .001). There were 17 (44%) men in the IR group and 26 (48%) men in the NIR group. Mean blood glucose at baseline before starting the infusion was 131.82 ± 49.55 mg/dL in IR patients and 106.16 ± 59.01 mg/dL in NIR patients ( P = .03). In the stepwise multivariate analysis for assessing the risk for developing hyperglycemia, HR for age was 1.020 (1.010-1.031), P < .001. CONCLUSIONS: Hyperglycemia is a common finding with the use of PN in both the hospital and ambulatory setting in patients without a previous diagnosis of DM2. Age was the most significant predictor of the requirement of insulin in the present study. When hyperglycemia is managed appropriately with insulin therapy, the long-term complications can be minimized.

Correction of hypovolemia with crystalloid fluids: Individualizing infusion therapy.

Many situations in clinical practice involving patients with hypovolemia or acutely ill patients usually require the administration of intravenous fluids. Current evidence shows that the use of crystalloids should be considered, since most colloids and human albumin are usually associated with increased adverse effects and high cost, respectively. Among crystalloids, the use of normal saline is implicated with the development of hyperchloremic metabolic acidosis and renal vasoconstriction. These observations have led many authors to propose balanced solutions, mainly Lactated Ringer's, as the infusate of choice. However, although the restoration of volume status is the primary target in hypovolemic state, the correction of any associated acid-base or electrolyte disorders that frequently coexist is also of vital importance. This review presents specific situations that are common in daily clinical practice and require targeted infusate therapy in patients with reduced volume status. Furthermore, the review presents an algorithm aiming to help clinicians to make the best choice between normal or hypotonic saline and lactated Ringer's infusates. Lactated Ringer's infusate should not be given in patients with severe metabolic alkalosis, lactic acidosis with decreased lactate clearance, or severe hyperkalemia, and in patients with traumatic brain injury or at risk of increased intracranial pressure. The optimal choice of infusate should be guided by the cause of hypovolemia, the cardiovascular state of the patient, the renal function, as well as the serum osmolality and the coexisting acid-base and electrolyte disorders. Clinicians should be aware of any coexisting disorders in patients with hypovolemia and guide their choice of infusate treatment based on the overall picture of their patients.