The impact of palliative care on quality of life, anxiety, and depression in idiopathic pulmonary fibrosis: a randomized controlled pilot study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal disease that results in poor quality of life due to progressive respiratory symptoms, anxiety, and depression. Palliative care improves quality of life and survival in other progressive diseases. No randomized controlled trials have investigated the impact of palliative care on quality of life, anxiety, or depression in IPF. METHODS: We conducted a randomized, controlled, pilot study to assess the feasibility of measuring the effect of a palliative care clinic referral on quality of life, anxiety, and depression in IPF. Patients were randomized to usual care (UC) or usual care + palliative care (UC + PC) with routine pulmonary follow up at 3 and 6 months. The UC + PC group received a minimum of one PC clinic visit. Primary outcome was change from baseline in quality of life, anxiety, and depression as measured by the St. George's Respiratory Questionnaire (SGRQ), the Hospital Anxiety and Depression Index (HADS), and the Patient Health Questionnaire (PHQ-9) at 6 months. RESULTS: Twenty-two patients were randomized between September 2017 through July 2018; 11 to UC and 11 to UC + PC. There was no difference in the change in SGRQ score at 3 months or 6 months, however, the symptom score trended towards a significant worsening for UC + PC at both 3 and 6 months (mean change at 3 months for UC and UC + PC was - 7.8 and + 10.7, respectively, p = 0.066; mean change at 6 months for UC and UC + PC was - 6.0 and + 4.6, respectively, p = 0.055). There was no difference in the change in HADS anxiety or depression scores. There was a significant transient worsening in PHQ-9 scores for UC + PC at 3 months (UC: -1.6, UC + PC: + 0.9, p = 0.008); this effect did not persist at 6 months. CONCLUSION: This pilot study demonstrated that a randomized controlled trial of palliative care in idiopathic pulmonary fibrosis patients is feasible. Receiving palliative care did not lead to improved quality of life, anxiety, or depression compared to usual care after 6 months. Patients in the UC + PC group trended towards worsening symptoms and a small but statistically significant transient worsening in depression. These findings should be interpreted with caution, and need to be evaluated in adequately powered clinical trials. NCT03981406, June 10, 2019, retrospectively registered.

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial.

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. We are developing biomaterials for craniomaxillofacial bone defects that are often large and irregularly shaped. These require close conformal contact between implant and defect margins to aid healing. While we have identified a mineralized collagen scaffold that promotes mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, its mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients.

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial.

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. Repairing craniomaxillofacial bone defects, which are often large and irregularly shaped, requires close conformal contact between implant and defect margins to aid healing. While mineralized collagen scaffolds can promote mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, their mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients. STATEMENT OF SIGNIFICANCE: Biomaterial strategies for (craniomaxillofacial) bone regeneration are often limited by the size and complex geometry of the defects. Voronoi structures are open-cell foams with tunable mechanical properties which have primarily been used computationally. We describe generative design strategies to create Voronoi foams via 3D-printing then embed them into an osteogenic mineralized collagen scaffold to form a multi-scale composite biomaterial. Voronoi structures have predictable and tailorable moduli, permit stain localization to defined regions of the composite, and permit conformal fitting to effect margins to aid surgical practicality and improve host-biomaterial interactions. Multi-scale composites based on Voronoi foams represent an adaptable design approach to address significant challenges to large-scale bone repair.

Propionibacterium acnes Causing Mediastinal Infection following Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is now a standard of care to sample mediastinal lymph nodes and masses with high diagnostic accuracy and low complication rates. However, the procedure has potential complications that might be life-threatening. Here, we present the first case of Propionobacterium acnes (P. acnes) causing mediastinitis following EBUS-TBNA of a subcarinal lymph node.

Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric.

BACKGROUND: Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the betaGeo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice. RESULTS: Optic nerve degeneration, characterized by axon loss and gliosis is first apparent in mice between 8 and 9 months of age. Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe. Although nerve damage is typically bilateral, the progression of disease is asymmetric between the eyes of individual mice. Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region. Ganglion cell loss, as a function of the loss of betaGeo expression, is evident in some mice between 8 and 10 months of age and is prevalent in the majority of mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells throughout the retina, but many younger mice exhibit focal loss of cells in sectors extending from the optic nerve head to the retinal periphery. Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal. CONCLUSION: A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma.

Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient.

Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

Nuclear atrophy of retinal ganglion cells precedes the bax-dependent stage of apoptosis.

PURPOSE: Retinal ganglion cells atrophy during the execution of the intrinsic apoptotic program. This process, which has been termed the apoptotic volume decrease (AVD) in other cell types, has not been well-characterized in ganglion cells. METHODS: Acute optic nerve crush was used to examine neuronal atrophy in the ganglion cell layer in wild-type and Bax-deficient mice. Nuclear size was measured from retinal wholemounts. Heterochromatin formation was assessed using transmission electron microscopy, whereas histone H4 acetylation was monitored using immunofluoresence. Ganglion cell and retinal transcript abundance was measured using quantitative PCR. RESULTS: Nuclear and soma sizes linearly correlated in both control and damaged retinas. Cells in wild-type mice exhibited nuclear atrophy within 1 day after optic nerve damage. Three days after crush, nuclear atrophy was restricted to ganglion cells identified by retrograde labeling, while amacrine cells also exhibited some atrophy by 5 days. Similar kinetics of nuclear atrophy were observed in cells deficient for the essential proapoptotic gene Bax. Bax-deficient cells also exhibited other nuclear changes common in wild-type cells, including the deacetylation of histones, formation of heterochromatin, and the silencing of ganglion cell-specific gene expression. CONCLUSIONS: Retinal ganglion cell somas and nuclei undergo the AVD in response to optic nerve damage. Atrophy is rapid and precedes the Bax-dependent committed step of the intrinsic apoptotic pathway.