Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP-2 Peptides for Cranial Bone Regeneration

Abstract

An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP-2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA-collagen-gelatin and Sr–Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP-2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical-sized defects created in rat calvariae. A sustained release of E7-BMP-2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X-ray microcomputed tomography (µ-CT) analysis reveal greater bone volume and bone formation area in case of the E7-BMP-2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP-2 mimicking peptide for cranial bone tissue regeneration.

This study reports novel 3D hybrid nanofiber aerogels that topically deliver trace metal ions and bone morphogenetic protein 2 peptides to promote neovascularization and cranial bone regeneration.

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Point-of-Care Identification of Bacteria Using Protein-Encapsulated Gold Nanoclusters

Abstract

The rapid, simple, and reliable identification of the most prevalent pathogens is essential for clinical diagnostics, biology, and food safety. Herein, four protein-encapsulated gold nanoclusters (protein–AuNCs) are designed and prepared as a sensor array for rapid identification of bacteria. The discrimination of six kinds of bacteria, including two kinds of drug-resistant bacteria, is successfully realized by the as-fabricated sensor array. The strategy presented here shows the advantages of easy synthesis and convenient to use. Furthermore, 100% classification accuracy is achieved by the sensor array consisting of two protein–AuNCs probes, demonstrating the design with sufficient diagnostic capacity. Taken together, the developed sensor array holds great promise for facile diagnosis of bacterial infection in resource-limited settings.

Four protein-encapsulated gold nanoclusters with various binding affinities to bacteria are employed as sensor array to rapid identification of bacteria. Two kinds of the most prevalent pathogens and their drug-resistant strains are well discriminated. The protocol holds great promise for point-of-care bacterial infection diagnosis because of the simple probe synthesis and bacterial identification procedures.

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Noninvasive Ventilation in Patients With Do-Not-Intubate and Comfort-Measures-Only Orders: A Systematic Review and Meta-Analysis

Objectives: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders. Data Sources: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017. Study Selection: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders. Data Extraction: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale. Data Synthesis: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49–64%) at hospital discharge and 32% (95% CI, 21–45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients with malignancy. Survival was comparable for patients treated in a hospital ward versus an ICU. Quality of life of survivors was not reduced compared with baseline, although few studies evaluated this. No studies evaluated quality of dying in nonsurvivors. In patients with comfort-measures-only orders, a single study showed that noninvasive ventilation was associated with mild reductions in dyspnea and opioid requirements. Conclusions: A large proportion of patients with do-not-intubate orders who received noninvasive ventilation survived to hospital discharge and at 1 year, with limited data showing no decrease in quality of life in survivors. Provision of noninvasive ventilation in a well-equipped hospital ward may be a viable alternative to the ICU for selected patients. Crucial questions regarding quality of life in survivors, quality of death in nonsurvivors, and the impact of noninvasive ventilation in patients with comfort-measures-only orders remain largely unanswered. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: wilson.michael1@mayo.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Short-Latency Positive Peak Following N20 Somatosensory Evoked Potential Is Superior to N20 in Predicting Neurologic Outcome After Out-of-Hospital Cardiac Arrest

Objectives: The absence of N20 somatosensory evoked potential after cardiac arrest is related to poor outcome. However, discrimination between the low-amplitude and the absence of N20 is challenging. P25 and P30 are short-latency positive peaks with latencies between 25 and 30 ms following N20 (P25/30). P25/30 is evident even with an ambiguous N20 in patients with good outcome. Therefore, we evaluated the predictive value of P25/30 after cardiac arrest. Design: A retrospective observational study. Setting: University-affiliated hospital. Subjects: Comatose survivors after out-of-hospital cardiac arrest treated by hypothermic targeted temperature management. Intervention: None. Measurements and Main Results: The specificity and the positive predictive value of P25/30 and N20 in predicting poor outcome were the same, showing a rate of 100%. The sensitivity of P25/30 in predicting poor outcome (90.12% [95% CI, 81.5–95.6%]) was higher than that of N20 (70.37% [95% CI, 59.2–80%]). Also, the negative predictive value of P25/30 in predicting poor outcome (81.4% [95% CI, 69.4–89.4%]) was higher than that of N20 (59.3% [95% CI, 51–67.1%]). The P25/30-based adjusted model showed a larger area under the curve (0.98 [95% CI, 0.95–1]) compared with the N20-based adjusted model (0.95 [95% CI, 0.91–0.98]) (p = 0.02). Conclusions: The absence of P25/30 is related to poor outcome with a higher sensitivity, negative predictive value than the absence of N20. This work was performed at Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu-si, Republic of Korea. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/29S62lw). A full list of the Cerebral Resuscitation and Outcome evaluation Within catholic Network (CROWN) Investigators can be found in Appendix 1. The statistical analysis was supported by a grant of the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HI14C1062). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: erkeeper@catholic.ac.kr Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Ultrasound-Guided Laryngeal Air Column Width Difference as a New Predictor for Postextubation Stridor in Children

Objectives: To assess the efficacy of ultrasound-guided laryngeal air column width difference in predicting postextubation stridor in children. Design: Prospective observational study. Setting: Single, tertiary care pediatric hospital. Patients: This study was carried out at PICU and surgical ICU, Tanta University Hospital on 400 ventilated children between January 2015 and May 2017. Patients who received mechanical ventilation and met criteria for a weaning trial were included. Intervention: Laryngeal ultrasound and cuff leak test. Measurements and Main Results: Ultrasound-guided laryngeal air column width and cuff leak test were measured before extubation. Laryngeal air column width is the width of air between the vocal cords seen by laryngeal ultrasonography. Laryngeal air column width difference is the width difference of air column passed through vocal cords with the balloon cuff inflated and deflated. Three-hundred fifty six patients (89%) had no postextubation stridor, whereas 44 patients (11%) developed postextubation stridor. Postextubation stridor was associated with younger age, less weight, female gender, prolonged duration of intubation, and ICU stay (p

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Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal

Objectives: To compare the international normalized ratio normalization efficacy of activated prothrombin complex concentrates and 4-factor prothrombin complex concentrates and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage. Design: Retrospective, Multicenter Cohort. Setting: Large, Community, Teaching Hospital. Patients: Patients greater than 18 years old and received either activated prothrombin complex concentrate or 4-factor prothrombin complex concentrate for the treatment of warfarin-associated hemorrhage. We excluded those patients who received either agent for an indication other than warfarin-associated hemorrhage, pregnant, had a baseline international normalized ratio of less than 2, received a massive transfusion as defined by hospital protocol, received plasma for treatment of warfarin-associated hemorrhage, or were treated for an acute warfarin ingestion. Interventions: Patients in the activated prothrombin complex concentrate group (enrolled from one hospital) with an international normalized ratio of less than 5 received 500 IU and those with an international normalized ratio greater than 5 received 1,000 IU. Patients in the 4-factor prothrombin complex concentrate (enrolled from a separate hospital) group received the Food and Drug Administration approved dosing algorithm. Measurements and Main Results: A total of 158 patients were included in the final analysis (activated prothrombin complex concentrate = 118; 4-factor prothrombin complex concentrate = 40). Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment international normalized ratio (2.7 ± 1.8 vs 3.5 ± 2.9; p = 0.0164). However, the posttreatment international normalized ratio was similar between the groups. In addition, even when controlling for differences in the pretreatment international normalized ratio, there was no difference in the ability to achieve a posttreatment international normalized ratio of less than 1.4 (odds ratio, 0.753 [95% CI, 0.637–0.890]; p = 0.0009). Those in the activated prothrombin complex concentrate group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23 [95% CI, 1.34–7.81]; p = 0.0088). There was only one posttreatment thrombotic complication reported. Conclusions: A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events. This work was completed at The University of Tennessee Medical Center in Knoxville, TN, and Saint Joseph's Hospital in Tampa, FL. Dr. Rowe received funding from The Medicine's Company and Chiesi. Drs. Rowe and Dietrich disclosed off-label product use of FEIBA use in warfarin-associated coagulopathy. Dr. Phillips disclosed off-label product use of Activated Prothrombin complex concentrate, which has been studied for reversal of Vitamin K-antagonist reversal but has not been approved by the U. S. Food and Drug Administration for this use. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: arowe@uthsc.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study

Objectives: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. Design: Harmonized data from prospective multicenter international longitudinal cohort studies Setting: Diverse mix of ICUs. Patients: Critically ill patients expected to be ventilated for longer than 24 hours. Interventions: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. Measurements and Main Results: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47–8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15–1.46]; p

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