3D printing of gellan-dextran methacrylate IPNs in glycerol and their bioadhesion by RGD derivatives.

The ever-growing need for new tissue and organ replacement approaches paved the way for tissue engineering. Successful tissue regeneration requires an appropriate scaffold, which allows cell adhesion and provides mechanical support during tissue repair. In this light, an interpenetrating polymer network (IPN) system based on biocompatible polysaccharides, dextran (Dex) and gellan (Ge), was designed and proposed as a surface that facilitates cell adhesion in tissue engineering applications. The new matrix was developed in glycerol, an unconventional solvent, before the chemical functionalization of the polymer backbone, which provides the system with enhanced properties, such as increased stiffness and bioadhesiveness. Dex was modified introducing methacrylic groups, which are known to be sensitive to UV light. At the same time, Ge was functionalized with RGD moieties, known as promoters for cell adhesion. The printability of the systems was evaluated by exploiting the ability of glycerol to act as a co-initiator in the process, speeding up the kinetics of crosslinking. Following semi-IPNs formation, the solvent was removed by extensive solvent exchange with HEPES and CaCl2, leading to conversion into IPNs due to the ionic gelation of Ge chains. Mechanical properties were investigated and IPNs ability to promote osteoblasts adhesion was evaluated on thin-layer, 3D-printed disk films. Our results show a significant increase in adhesion on hydrogels decorated with RGD moieties, where osteoblasts adopted the spindle-shaped morphology typical of adherent mesenchymal cells. Our findings support the use of RGD-decorated Ge/Dex IPNs as new matrices able to support and facilitate cell adhesion in the perspective of bone tissue regeneration.

Polysaccharide-Based Nanogels to Overcome Mucus, Skin, Cornea, and Blood-Brain Barriers: A Review.

Nanocarriers have been extensively developed in the biomedical field to enhance the treatment of various diseases. However, to effectively deliver therapeutic agents to desired target tissues and enhance their pharmacological activity, these nanocarriers must overcome biological barriers, such as mucus gel, skin, cornea, and blood-brain barriers. Polysaccharides possess qualities such as excellent biocompatibility, biodegradability, unique biological properties, and good accessibility, making them ideal materials for constructing drug delivery carriers. Nanogels, as a novel drug delivery platform, consist of three-dimensional polymer networks at the nanoscale, offering a promising strategy for encapsulating different pharmaceutical agents, prolonging retention time, and enhancing penetration. These attractive properties offer great potential for the utilization of polysaccharide-based nanogels as drug delivery systems to overcome biological barriers. Hence, this review discusses the properties of various barriers and the associated constraints, followed by summarizing the most recent development of polysaccharide-based nanogels in drug delivery to overcome biological barriers. It is expected to provide inspiration and motivation for better design and development of polysaccharide-based drug delivery systems to enhance bioavailability and efficacy while minimizing side effects.

Exploring physician gender bias in the initiation of prescribing cascades for older men and women: a qualitative clinical vignette study protocol.

INTRODUCTION: A prescribing cascade occurs when a drug is prescribed to manage the often unrecognised side effect of another drug; these cascades are of particular concern for older adults who are at heightened risk for drug-related harm. It is unknown whether, and to what extent, gender bias influences physician decision-making in the context of prescribing cascades. The aim of this transnational study is to explore the potential impact of physician implicit gender biases on prescribing decisions that may lead to the initiation of prescribing cascades in older men and women in two countries, namely: Canada and Italy. METHODS AND ANALYSIS: Male and female primary care physicians at each site will be randomised 1:1 to a case vignette that features either a male or female older patient who presents with concerns consistent with the side effect of a medication they are taking. During individual interviews, while masked to the true purpose of the study, participants will read the vignette and use the think-aloud method to describe their ongoing thought processes as they consider the patient's concerns and determine a course of action. Interviews will be recorded, transcribed verbatim and thematic analysis will be conducted to highlight differences in decisions in the interviews/transcripts, using a common analytical framework across the sites. ETHICS AND DISSEMINATION: This study has received ethics approval at each study site. Verbal informed consent will be received from participants prior to data collection and all data will be deidentified and stored on password-protected servers. Results of this study will be disseminated through peer-reviewed journal articles and presented at relevant national and international conferences.

Safety and Tolerability of Antimicrobial Agents in the Older Patient.

Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug-drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.

Disparities in Lung Transplant among Patients with Idiopathic Pulmonary Fibrosis: An Analysis of the IPF-PRO Registry.

Rationale: Lung transplant offers the potential to extend life for patients with idiopathic pulmonary fibrosis (IPF); yet, this therapeutic modality is only available to a small proportion of patients. Objectives: To identify clinical characteristics and social determinants of health that differentially associate with lung transplant compared with death in patients with IPF. Methods: We evaluated data from the Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry, a multicenter U.S. registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Patients were enrolled between June 2014 and October 2018. Patients who were listed for lung transplant were not eligible to enroll in the registry, but patients could be listed for transplant after enrollment. We performed a multivariable time-to-event analysis incorporating competing risks methodology to examine differential associations between prespecified covariates and the risk of lung transplant versus death. Covariates included factors related to lung transplant eligibility, clinical characteristics of IPF, and social determinants of health. Covariates were modeled as time independent or time dependent as appropriate. Results: Among 955 patients with IPF, event rates of lung transplant and death were 7.4% and 16.3%, respectively, at 2 years. Covariates with the strongest differential association were age, median zip code income, and enrollment at a center with a lung transplant program. Lung transplant was less likely (hazard ratio [HR], 0.13 [95% confidence interval (CI), 0.06-0.28] per 5-yr increase) and death more likely (HR, 1.41 [95% CI, 1.22-1.64] per 5-yr increase) among those older than 70 years of age. Higher median zip code income was associated with lung transplant (HR, 1.22 [95% CI, 1.13-1.31] per $10,000 increase) but not death (HR, 0.99 [95% CI, 0.94-1.04] per $10,000 increase). Enrollment at a center with a lung transplant program was associated with lung transplant (HR, 4.31 [95% CI, 1.76-10.54]) but not death (HR, 0.99 [95% CI, 0.69-1.43]). Oxygen use with activity was associated with both lung transplant and death, but more strongly with lung transplant. A higher number of comorbidities was associated with an increased likelihood of death but not lung transplant. Conclusions: For patients in the Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry, median zip code income and access to a lung transplant center differentially impact the risk of lung transplant compared with death, regardless of disease severity measures or other transplant eligibility factors. Interventions are needed to mitigate inequalities in lung transplantation based on socioeconomic status. Clinical trial registered with www.clinicaltrials.gov (NCT01915511).

The Role of Surgical Lung Biopsy in the Diagnosis of Fibrotic Interstitial Lung Disease: Perspective from the Pulmonary Fibrosis Foundation.

Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary discussion approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathologic specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in patients with ILD. This document was developed by the SLB Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians, including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD; outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD; and provide practical information to maximize the yield and safety of SLB.

Oropharyngeal swallow physiology and swallowing-related quality of life in underweight patients with concomitant advanced chronic obstructive pulmonary disease.

Background: Swallowing impairment (dysphagia) has been associated with COPD and may contribute to exacerbations of this chronic and progressive disease. Further, risk of mortality increases with concomitant presence of cachexia in the COPD population. The purpose of this prospective study was to depict oropharyngeal swallowing physiology in underweight patients with stable but advanced-stage COPD. Patients and methods: Ten underweight patients with stable but advanced COPD underwent a modified barium swallow study. Analysis of oropharyngeal swallowing function was completed using the standardized Modified Barium Swallow Impairment Profile and the Penetration-Aspiration Scale. Scores from the Dysphagia Handicap Index and 10-item Eating Assessment Tool were collected to assess patient perception of swallowing difficulty. Findings were compared to age- and sex-matched healthy controls. Results: Significantly higher MBSImP oral total scores (P=0.007) were observed in COPD patients compared to matched controls, but no difference was observed in pharyngeal total scores (P=0.105). Patients with COPD had significantly higher maximum PAS scores compared with controls (P=0.030). There was no significant difference in EAT-10 or DHI scores between patients with COPD and controls (P=0.41 and P=0.08, respectively). Conclusion: Underweight patients with severe but stable COPD present with dysphagia that may not be recognized by the patient. Further investigation is needed to elucidate the interaction between the respiratory-swallowing systems, how muscular weakness may contribute to swallowing impairment, and responsiveness to swallowing treatment.

Closure of a Post-Transplant Bronchial Dehiscence With Endobronchial Fibrin Sealant.

Airway complications after lung transplantation are well described and can lead to significant morbidity and mortality. Treatment options for anastomotic dehiscence include expectant management, placement of endobronchial stents, or surgical repair. The use of fibrin sealant instilled by bronchoscopy to seal a dehiscence has not been well described. Our patient is a 57-year-old man who underwent orthotropic bilateral lung transplantation for end-stage chronic obstructive pulmonary disease. He was found to have a partial bronchial anastomosis dehiscence and was subsequently treated with endobronchial fibrin sealant glue instillation. This case illustrates the successful use of endobronchial fibrin sealant for bronchial anastomosis dehiscence.

Lung Donation After Death Resulting From a Stanford Type A Aortic Dissection.

The number of lung transplantations performed in the United States has increased at a modest pace over the past decades and reached an all-time high of 2,052 in 2015. However, the transplant wait list mortality remains unacceptably high with approximately one in five patients removed from the list because of death or being too sick for transplantation. The greatest limitation to performing lung transplantations is the relative lack of acceptable lung donors. Here we report the use of lungs from a donor who died as the result of adverse events related to a Stanford type A aortic dissection.

The utility of nodule volume in the context of malignancy prediction for small pulmonary nodules.

BACKGROUND: An estimated 150,000 pulmonary nodules are identified each year, and the number is likely to increase given the results of the National Lung Screening Trial. Decision tools are needed to help with the management of such pulmonary nodules. We examined whether adding any of three novel functions of nodule volume improves the accuracy of an existing malignancy prediction model of CT scan-detected nodules. METHODS: Swensen's 1997 prediction model was used to estimate the probability of malignancy in CT scan-detected nodules identified from a sample of 221 patients at the Medical University of South Carolina between 2006 and 2010. Three multivariate logistic models that included a novel function of nodule volume were used to investigate the added predictive value. Several measures were used to evaluate model classification performance. RESULTS: With use of a 0.5 cutoff associated with predicted probability, the Swensen model correctly classified 67% of nodules. The three novel models suggested that the addition of nodule volume enhances the ability to correctly predict malignancy; 83%, 88%, and 88% of subjects were correctly classified as having malignant or benign nodules, with significant net improved reclassification for each (P<.0001). All three models also performed well based on Nagelkerke R2, discrimination slope, area under the receiver operating characteristic curve, and Hosmer-Lemeshow calibration test. CONCLUSIONS: The findings demonstrate that the addition of nodule volume to existing malignancy prediction models increases the proportion of nodules correctly classified. This enhanced tool will help clinicians to risk stratify pulmonary nodules more effectively.

Current status of tobacco policy and control.

Behaviors pertaining to tobacco use have changed significantly over the past century. Compared with 1964, smoking prevalence rates have halved from 40% to 20%, and as a result there has been a slow but steady decline in the rates of tobacco-induced diseases such as heart disease and cancer. Growing awareness of the health risks of smoking was aided by the US Surgeon Reports that were issued on a nearly annual basis starting from 1964. Concerns about the hazards of breathing in second-hand smoke further contributed to the declining social acceptance of smoking, which evolved into regulatory actions restricting smoking on buses, planes, retail outlets, restaurants, and bars. Today, 23 states and 493 localities have comprehensive laws restricting indoor smoking. This paper examines public policies that have made a significant impact on smoking and lung cancer rates and discusses potential future research directions to further reduce the diseases caused by smoking.

A decade of advances in treatment of early-stage lung cancer.

Emerging from the past decade, there has been a diversification of options for the treatment of early-stage lung cancer. Video-assisted thoracoscopic surgery is now more widely performed, with oncologic outcomes equivalent to those with open thoracotomy. Although lobectomy remains the standard approach to surgical resection, lesser resections, such as segmentectomy and wedge resection, are considerations for some patients. Advances in surgical, radiation, and medical therapies continue to evolve. Future research questions will focus on comparing long-term outcomes with these modalities, including survival, as well as patient-centered endpoints, such as quality of life.