Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines.

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH2), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH2) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.

A Novel Silicon Device for the Packing of Cutaneous Abscesses.

BACKGROUND: Superficial skin abscesses are commonly encountered in emergency medicine practice. Standard treatment includes incision, drainage, and often packing with a gauze strip. The packing component of the procedure has several negative potential outcomes, is painful, and necessitates a return visit for removal. DISCUSSION: Here we report the first case in which a novel silicon packing device was utilized. The patient presented with a facial abscess, which was incised and drained. The novel device was inserted, and removed by the patient independently, without complication. Both patient and provider reported satisfaction with the novel procedure, and noted low pain scores. CONCLUSIONS: This device has the potential to replace traditional packing, and will require further study through a controlled trial to assess for safety and efficacy.

Contrast Extravasation as a Complication of Emergency Nurse-Performed Ultrasound-Guided Peripheral Intravenous Catheter Placement.

INTRODUCTION: Vascular access procedures are among the most commonly performed procedures in the emergency department. The objective of the current study was to compare the contrast extravasation rate for ultrasound-guided peripheral intravenous (USGPIV) catheter placement by emergency nurses with peripheral intravenous catheters placed by standard landmark techniques. METHODS: A retrospective chart review of all ED patients at our urban tertiary-care institution who underwent contrasted computed tomography examination and suffered contrast extravasation events was performed. A logbook of all ED patients who underwent USGPIV placement and an institution-wide electronic patient safety incident-reporting system was reviewed for all contrast extravasation events between May 2014, and February 2017. Data were analyzed using descriptive statistics, Student t-tests for continuous data, and χ2 or Fisher's exact test for categorical data. RESULTS: One thousand five hundred USGPIV catheters were placed by 27 emergency nurses. Contrast material was administered 29,508 times, and, of these, 291 were administered via USGPIV placement. There were 74 peripheral IV lines with documented contrast extravasations (0.25%) as reported in the safety-event database; 12 (4.1%) were from the USGPIV population, and 62 (0.21%) occurred in the standard landmark technique population. Relative risk of contrast extravasation events with USGPIV placement was 19.4 (95% confidence interval [CI], 10.6-35.6), and the absolute risk difference was 3.9% (95% CI 1.6%-6.2%). DISCUSSION: USGPIV placement by trained emergency nurses has higher rates of contrast extravasation than with standard landmark technique placement.

Removing Barriers to Emergency Medicine Point-of-Care Ultrasound: Illustrated by a Roadmap for Emergency Medicine Point-of-Care Ultrasound Expansion in India.

Point-of-care ultrasound (PoCUS) has a potentially vital role to play in emergency medicine (EM), whether it be in high-, medium-, or low-resourced settings. However, numerous barriers are present which impede EM PoCUS implementation nationally and globally: (i) lack of a national practice guideline or scope of practice for EM PoCUS, (ii) resistance from non-PoCUS users of ultrasound imaging (USI) and lack of awareness from those who undertake parallel or post-EM patient care, and (iii) heterogeneous pattern of resources available in different institutes and settings. When combined with the Indian Preconception and Prenatal Diagnostic Techniques (PCPNDT) Act, this has led to the majority of India's 1.4 billion citizens being unable to access EM PoCUS. In order to address these barriers (globally as well as with specific application to India), this article outlines the three core principles of EM PoCUS: (i) the remit of the EM PoCUS USI must be well defined a priori, (ii) the standard of EM PoCUS USI must be the same as that of non-PoCUS users of USI, and (iii) the imaging performed should align with subsequent clinical decision-making and resource availability. These principles are contextualized using an integrated PoCUS framework approach which is designed to provide a robust foundation for consolidation and expansion across different PoCUS specialisms and health-care settings. Thus, a range of mechanisms (from optimization of clinical practice through to PoCUS educational reform) are presented to address such barriers. For India, these are combined with specific mechanisms to address the PCPNDT Act, to provide the basis for influencing national legislation and instigating an addendum to the Act. By mapping to the recent Lancet Commission publication on transforming access to diagnostics, this provides a global and cross-discipline perspective for the recommendations.

Outcomes of Ultrasound Guided Peripheral Intravenous Catheters Placed in the Emergency Department and Factors Associated with Survival.

Background: Patients with difficult peripheral intravenous (IV) access are common in emergency departments (EDs). Ultrasound-guided peripheral intravenous catheters (USIVs) are frequently used in this population; however, information regarding the effect of patient and IV characteristics on the dwell time (DT) and survival probability (SP) of USIVs is limited. Objective: Our study aimed to evaluate for associations between patient or IV characteristics and the DT and SP of USIVs. Methods: Retrospective analysis was performed on a database from an ED nurse (RN) USIV training program at an urban, academic hospital. Patients over 18 years with an USIV placed during the study period were included. Subject demographics, history, IV characteristics, insertion, and removal times were collected. Data were analyzed using descriptive statistics and univariable and multivariable Cox regression. USIV survival times for variates of interest were estimated using Kaplan-Meier curves for three censoring points. Results: The final analysis cohort was 388 patients. Mean age was 56.6 years, 66.5% were female, mean BMI was 29.9 kg/m2, and 42.5% were obese (BMI ≥30). Median DT was 40.3 hours in admitted patients (N=340). SP for USIVs at 96 hours was 87.8%. A total of 21 of 340 (6.2%) USIVs failed. USIV location conferred a difference on DT in obese patients when dichotomized into upper arm versus antecubital fossa and forearm together (38.6 hours vs 44.6 hours, p=0.03). No factors were associated with a difference in USIV SP. Conclusion: Median USIV DT of 40.3 hours for admitted patients was higher than in previous studies. Only 7% of USIVs in our study failed. Overall, catheters survived longer than expected.

Randomized Controlled Trial of a Novel Silicone Device for the Packing of Cutaneous Abscesses in the Emergency Department: A Pilot Study.

OBJECTIVE: Traditional treatment of abscesses in the emergency department includes packing with gauze; however, this can add pain and discomfort to the procedure and frequently involves a follow-up visit for packing removal. Alternatives to gauze packing have been proposed, but they may have disadvantages in the context of emergency care. The objective of this pilot study was to investigate the use of a novel silicone packing device - the Derma-Stent. METHODS: This was a randomized controlled pilot study of 50 patients from two urban emergency departments with uncomplicated superficial abscesses. The primary outcome was the likelihood of self-removal of packing gauze versus the silicone device. Secondary outcome measures included subjective clinician and patient metrics, such as pain and ease of use. RESULTS: Patients identified with simple cutaneous abscesses were randomized to intervention (packing with the novel silicone device, n=25) or standard care (gauze packing, n=25). Mean age was 36 years, 54% were female, and 96% identified as African American. Although it took longer to place, the silicone device (19.0 vs 15.3 minutes, p=0.03), pain scores were significantly lower (4.3/10 vs 7.1/10, p=0.008) and ease of use reported by physicians better in the silicone-device group (4.8/5 vs 4.0/5, p=0.002). A high unknown rate in the gauze-packing group limits discussion of the likelihood of self-removal; however, the silicone device was more likely to remain in place (60%) versus the gauze packing at 3 days (24%, p=0.01). CONCLUSION: This pilot randomized controlled trial compared the treatment of packing cutaneous abscesses with gauze versus using the silicone device. Limitations in the data prevent discussion on likelihood of self-removal. However, the silicone device was more likely to remain in place at day 3 follow-up and was equally effective to gauze packing in abscess reduction while also improving patient-reported pain scores. It did take longer to place the silicone device; however, physicians reported better ease of use and removal. This pilot study is encouraging for additional larger-scale trials that are required to further assess the utility of this device in the emergency department.

Housing R6/2 Mice with Wild-Type Littermates Increases Lifespan.

The R6/2 murine model of Huntington's disease (HD) is extensively used in HD research. The current study replicates and extends previous work assessing the impact of housing R6/2 mice with healthy wild-type (WT) littermates on disease progression. The current study extends the previous finding by including male cohorts and the use of a standard diet and water regimen, as opposed to the enhanced diet used in the previous study. This study found that the inclusion of healthy wild-type (WT) littermates, alone, improved survivabilty in R6/2 mice, but did not have a significant impact on weight loss.

Clinical experience with a chlorhexidine-coated PICC: A prospective, multicenter, observational study.

INTRODUCTION: This study evaluated a chlorhexidine-coated peripherally inserted central catheter (PICC) and the incidence of associated complications within both inpatient and outpatient populations. METHODS: This IRB-approved, multicenter, prospective observational study was performed at three large teaching hospitals in the US. All adults who required a PICC for ⩾14 days were considered. Patients were monitored throughout entire catheter dwell. Duplex venous ultrasounds were performed before insertion, after 10 to 14 days of dwell time, and upon removal. Data was collected from the hospital, outpatient clinic, and patient PICC diary records. RESULTS: A total of 103 patients, 56% male, with mean BMI 29 ± 8.8, were enrolled. The majority (79%) of patients were from high-risk groups-cancer, infectious diseases, transplant, and trauma. Primary treatment indications were antibiotics (66.99%) and chemotherapy (25.24%). Double lumen PICCs (59.2%) were favored clinically, as was basilic vein placement (71.84%). Mean catheter dwell was 47.01 ± 25.82 days. Three (3, 2.9%) central line-associated bloodstream infections (CLABSI) were reported. Four patients (4.6%) reported symptomatic catheter-related thrombosis (CRT), confirmed with ultrasound. Three patients (3.4%) had ultrasound-confirmed fibroblastic sleeve (FS). Eight patients (9.2%) who entered the study with pre-existing superficial thrombosis, had complete resolution at the time of catheter removal. The incidence of CLABSI was 0.82/1000 days. The combined CRT and FS rate was 6.9%. CONCLUSION: Based upon the observational findings of this study, chlorhexidine-coated PICC technology may be considered for use in patient populations who are at moderate to high-risk for catheter-related complications in both inpatient and outpatient settings.

PAMAM Dendrimer Nanomolecules Utilized as Drug Delivery Systems for Potential Treatment of Glioblastoma: A Systematic Review.

Glioblastoma (GB) is a grade IV astrocytoma that maintains a poor prognosis with respect to current treatment options. Despite major advancements in the fields of surgery and chemoradiotherapy over the last few decades, the life expectancy for someone with glioblastoma remains virtually unchanged and warrants a new approach for treatment. Poly(amidoamine) (PAMAM) dendrimers are a type of nanomolecule that ranges in size (between 1 and 100 nm) and shape and can offer a new viable solution for the treatment of intracranial tumors, including glioblastoma. Their ability to deliver a variety of therapeutic cargo and penetrate the blood-brain barrier (BBB), while preserving low cytotoxicity, make them a favorable candidate for further investigation into the treatment of glioblastoma. Here, we present a systematic review of the current advancements in PAMAM dendrimer technology, including the wide spectrum of dendrimer generations formulated, surface modifications, core modifications, and conjugations developed thus far to enhance tumor specificity and tumor penetration for treatment of glioblastoma. Furthermore, we highlight the extensive variety of therapeutics capable of delivery by PAMAM dendrimers for the treatment of glioblastoma, including cytokines, peptides, drugs, siRNAs, miRNAs, and organic polyphenols. While there have been prolific results stemming from aggressive research into the field of dendrimer technology, there remains a nearly inexhaustible amount of questions that remain unanswered. Nevertheless, this technology is rapidly developing and is nearing the cusp of use for aggressive tumor treatment. To that end, we further highlight future prospects in focus as researchers continue developing more optimal vehicles for the delivery of therapeutic cargo.

Resuscitation Guided by Volume Responsiveness Does Not Reduce Mortality in Sepsis: A Meta-Analysis.

Resuscitation with IV fluids is a critical component in the management of sepsis. Although the optimal volume of IV fluid is unknown, there is evidence that excessive administration can be deleterious. Static measures of volume status have not proven to be meaningful resuscitative endpoints. Determination of volume responsiveness has putative benefits over static measures, but its effect on outcomes is unknown. The goal of this systematic review and meta-analysis was to determine if resuscitation with a volume responsiveness-guided approach leads to improved outcomes in septic patients. DATA SOURCES: We searched PubMed, EMBASE, CINAHL, Web of Science, Cochrane Library, and Google Scholar from inception until April 2018. STUDY SELECTION: Prospective studies of patients with sepsis, severe sepsis, or septic shock that compared volume responsiveness-guided fluid resuscitation to standard techniques and reported mortality data. DATA EXTRACTION: We extracted study details, patient characteristics, volume responsiveness assessment method, and mortality data. DATA SYNTHESIS: Of the 1,224 abstracts and 31 full-texts evaluated, four studies (total 365 patients) met inclusion criteria. Using random effects modeling, the pooled odds ratio for mortality at time of longest follow-up with a volume responsiveness-guided strategy was 0.87 (95% CI, 0.49-1.54). Pooling of clinical data was not possibly owing to heterogeneity of reporting in individual studies. CONCLUSIONS: We found no significant difference in mortality between septic patients resuscitated with a volume responsiveness-guided approach compared with standard resuscitative strategies. It remains unclear whether the findings are due to the small sample size or a true lack of efficacy of a volume responsiveness-guided approach.

Inferior vena cava collapsibility loses correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure.

PURPOSE: Point-of-care ultrasound evaluates inferior vena cava (IVC) and internal jugular vein (IJV) measurements to estimate intravascular volume status. The reliability of the IVC and IJV collapsibility index during increased thoracic or intra-abdominal pressure remains unclear. METHODS: Three phases of sonographic scanning were performed: spontaneous breathing phase, increased thoracic pressure phase via positive pressure ventilation (PPV) phase, and increased intra-abdominal pressure (IAP) phase via laparoscopic insufflation to 15 mmHg. IVC measurements were done at 1-2 cm below the diaphragm and IJV measurements were done at the level of the cricoid cartilage during a complete respiratory cycle. Collapsibility index was calculated by (max diameter - min diameter)/max diameter × 100 %. Chi square, t test, correlation procedure (CORR) and Fisher's exact analyses were completed. RESULTS: A total of 144 scans of the IVC and IJV were completed in 16 patients who underwent laparoscopic surgery. Mean age was 46 ± 15 years, with 75 % female and 69 % African-American. IVC and IJV collapsibility correlated in the setting of spontaneous breathing (r (2) = 0.86, p < 0.01). IVC collapsibility had no correlation with the IJV in the setting of PPV (r (2) = 0.21, p = 0.52) or IAP (r (2) = 0.26, p = 0.42). Maximal IVC diameter was significantly smaller during increased IAP (16.5 mm ± 4.9) compared to spontaneous breathing (20.6 mm ± 4.8, p = 0.04) and PPV (21.8 mm ± 5.6, p = 0.01). CONCLUSION: IJV and IVC collapsibility correlated during spontaneous breathing but there was no statistically significant correlation during increased thoracic or intra-abdominal pressure. Increased intra-abdominal pressure was associated with a significant smaller maximal IVC diameter and cautions the reliability of IVC diameter in clinical settings that are associated with intra-abdominal hypertension or abdominal compartment syndrome.