Search

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies., Introduction Primary graft dysfunction (PGD) is a common early complication after lung transplantation that adversely affects both shortand long-term outcomes. This includes both early morbidity and mortality as well as [...]

Tertiary lymphoid organs are aggregates of immune and stromal cells including high endothelial venules and lymphatic vessels that resemble secondary lymphoid organs and can be induced at nonlymphoid sites during inflammation. The function of lymphatic vessels within tertiary lymphoid organs remains poorly understood. During lung transplant tolerance, [Foxp3.sup.+] cells accumulate in tertiary lymphoid organs that are induced within the pulmonary grafts and are critical for the local downregulation of alloimmune responses. Here, we showed that tolerant lung allografts could induce and maintain tolerance of heterotopic donor-matched hearts through pathways that were dependent on the continued presence of the transplanted lung. Using lung retransplantation, we showed that [Foxp3.sup.+] cells egressed from tolerant lung allografts via lymphatics and were recruited into donor-matched heart allografts. Indeed, survival of the heart allografts was dependent on lymphatic drainage from the tolerant lung allograft to the periphery. Thus, our work indicates that cellular trafficking from tertiary lymphoid organs regulates immune responses in the periphery. We propose that these findings have important implications for a variety of disease processes that are associated with the induction of tertiary lymphoid organs., Introduction Tertiary lymphoid organs can be induced in nonlymphoid tissues during states of chronic inflammation or antigen exposure and are structurally similar to secondary lymphoid organs. One such example is [...]

Application of nanotechnology is making huge progress in the biomedical and environmental fields. The design and production of nanoreactors based on the combination of catalytic properties of enzymes and the unique characteristics of nano-sized materials is, certainly, an opportunity to solve different challenges in biomedical and environmental fields. Most of the research efforts to combine enzymes and nanostructured materials have been made using ceramic, metallic, or carbon-based materials. Nevertheless, biomaterials, or materials from biological origin, have two main advantages for biomedical and environmental applications when compared with non-biological nanomaterials; they are biocompatible and biodegradable materials. In this work, a critical review of the literature information on nanostructured biomaterials for enzyme delivery is shown.

We present a combination of light-sheet excitation and two-dimensional fluorescence intensity ratio (FIR) measurements as a simple and promising technique for three-dimensional temperature mapping. The feasibility of this approach is demonstrated with samples fabricated with sodium yttrium fluoride nanoparticles co-doped with rare-earth ytterbium and erbium ions (NaYF4:Yb3+/Er3+) incorporated into polydimethylsiloxane (PDMS) as a host material. In addition, we also evaluate the technique using lipid-coated NaYF4:Yb3+/Er3+ nanoparticles immersed in agar. The composite materials show upconverted (UC) fluorescence bands when excited by a 980 nm near-infrared laser light-sheet. Using a single CMOS camera and a pair of interferometric optical filters to specifically image the two thermally-coupled bands (at 525 and 550 nm), the two-dimensional FIR and, hence, the temperature map can be readily obtained. The proposed method can take optically sectioned (confocal-like) images with good optical resolution over relatively large samples (up to the millimetric scale) for further 3D temperature reconstruction. [ABSTRACT FROM AUTHOR]

Composites of Ag and TiO2 nanoparticles were synthesized in situ on cotton fabrics using sonochemical and solvothermal methods achieving the successive formation of Ag-NPs and Ti-NPs directly on the fabric. The impregnated fabrics were characterized using ATR-FTIR spectroscopy; high-resolution microscopy (HREM); scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS); Raman, photoluminescence, UV-Vis, and DRS spectroscopies; and by tensile tension tests. Results showed the successful formation and impregnation of NPs on the cotton fabric, with negligible leaching of NPs after several washing cycles. The photocatalytic activity of supported NPs was assessed by the degradation of methyl blue dye (MB) under solar and UV irradiation revealing improved photocatalytic activity of the Ag–TiO2/cotton composites due to a synergy of both Ag and TiO2 nanoparticles. This behavior is attributed to a diminished electron–hole recombination effect in the Ag–TiO2/cotton samples. The biocide activity of these composites on the growth inhibition of Staphylococcus aureus (Gram+) and Escherichia coli (Gram−) was confirmed, revealing interesting possibilities for the utilization of the functionalized cotton fabric as protective cloth for medical applications. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is the leading cause of death in the first 30 days after lung transplantation and is also associated with worse long-term outcomes. Outcomes of patients with PGD grade 3 requiring extracorporeal membrane oxygenation (ECMO) support after lung transplantation have yet to be well described. We sought to describe short- and long-term outcomes for patients with PGD grade 3 who required ECMO support. This is a single-center retrospective cohort study of patients undergoing lung transplantation. We stratified patients with PGD grade 3 into non-ECMO, venoarterial (VA) ECMO, and venovenous (VV) ECMO groups after transplantation. We then compared the outcomes between the groups. Of 773 lung transplant recipients, PGD grade 3 developed in 204 (26%) at any time in the first 72 hours after lung transplantation. Of these, 13 (5%) required VA ECMO and 25 (10%) required VV ECMO support. The 30-day, 1-year, and 5-year survival in the VA ECMO group was 62%, 54%, and 43% compared with 96%, 84%, and 65% in the VV ECMO group and 99%, 94%, and 71% in the non-ECMO group. Multivariable Cox regression analysis showed that VA ECMO was associated with increased mortality (hazard ratio, 2.37; 95% CI, 1.06-5.28; P =.04). Patients who required VA ECMO support for PGD grade 3 have significantly worse survival compared with those who did not require ECMO and those who required VV ECMO support. This suggests that VA ECMO treatment of patients with PGD grade 3 after lung transplantation can be a predictable risk factor for mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). Background: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. Methods: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). Results: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). Conclusions: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population. [ABSTRACT FROM AUTHOR]

Background: Recent studies have suggested that more frequent post-operative surveillance imaging via computed tomography (CT) following lung cancer resection may not improve outcomes. We sought to validate these findings using a uniquely compiled dataset from the Veterans Health Administration, the largest integrated healthcare system in the United States.Methods: We performed a retrospective cohort study of Veterans with pathologic stage I non-small cell lung cancer (NSCLC) receiving surgery (2006-2016). We assessed the relationship between surveillance frequency (chest CT scans within 2 years after surgery) and recurrence-free survival and overall survival.Results: Among 6171 patients, 3047 (49.4%) and 3124 (50.6%) underwent low-frequency (<2 scans/year; every 6-12 months) and high-frequency (≥2 scans/year; every 3-6 months) surveillance, respectively. Factors associated with high-frequency surveillance included being a former smoker (vs. current, adjusted odds ratio [aOR] 1.18, 95% CI 1.05-1.33), receiving a wedge resection (vs. lobectomy, aOR 1.21, 95% CI 1.05-1.39), and having follow-up with an oncologist (aOR 1.58, 95% CI 1.42-1.77), whereas African American race was associated with low-frequency surveillance (vs. White race, aOR 0.64, 95% CI 0.54-0.75). With a median (IQR) follow-up of 7.3 (3.4-12.5) years, recurrence was detected in 1360 (22.0%) patients. High-frequency surveillance was not associated with longer recurrence-free survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.83-1.04, p = 0.22) or overall survival (aHR, 1.04; 95% CI, 0.96-1.12, p = 0.35).Conclusions: We found that high-frequency surveillance does not improve outcomes in surgically treated stage I NSCLC. Future lung cancer treatment guidelines should consider less frequent surveillance imaging in patients with stage I disease. [ABSTRACT FROM AUTHOR]

Multiple stakeholders have advocated for minimum volume standards for complex surgical procedures. The Leapfrog Group recommends that patients with non–small cell lung cancer (NSCLC) receive surgical resection at hospitals that perform at least 40 lung resections annually. However, the cost-effectiveness of this paradigm is unknown. A cost-effectiveness analysis was performed on 90-day and 5-year horizons for patients with clinical stage I NSCLC undergoing surgical resection at hospitals stratified by Leapfrog standard. Model inputs were derived from either the literature or a propensity score–matched cohort using the National Cancer Database. For the 5-year horizon, we simulated using a Markov model with 1-year cycle. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. For the 90-day horizon, resection at a Leapfrog hospital was more costly ($25 567 vs $25 530) but had greater utility (0.185 vs 0.181 quality-adjusted life-years), resulting in an ICER of 10 506. Similarly, for the 5-year horizon, resection at a Leapfrog hospital was more costly ($26 600 vs $26 495) but more effective (3.216 vs 3.122 quality-adjusted life-years), resulting in an ICER of 1108. When the costs for long-distance travel, lodging, and loss of productivity for caregivers were factored in, the ICER was 20 499 during the 5-year horizon for resection at Leapfrog hospitals. Using a willingness-to-pay threshold of $50 000, resection at a Leapfrog hospital remained cost-effective. Receiving surgery for clinical stage I NSCLC at hospitals that meet Leapfrog volume standards is cost-effective. Payers and policymakers should consider supporting patient and caregiver travel to higher volume institutions for lung cancer surgery. [ABSTRACT FROM AUTHOR]

Equitable access to care is a critical component of comprehensive surgical lung cancer management. Despite this, quality measures (QMs) assessing preoperative access to care are lacking. This study determined several preoperative QMs on the basis of contemporary treatment guidelines and hypothesized that poor access to care was associated with worse outcomes. This retrospective cohort study used a specially compiled Veterans Health Administration data set of patients with clinical stage I non-small cell lung cancer (NSCLC) who underwent surgical treatment (2006-2016). The study defined 4 QMs that patients with clinical stage I NSCLC should routinely meet in the preoperative period: timely surgery, positron emission tomography imaging, appropriate smoking management, and pulmonary function testing. The relationship between meeting these QMs and various short- and long-term outcomes was assessed. Among 9749 veterans undergoing surgery for clinical stage I NSCLC, 3371 (34.6%) met all QMs. Factors associated with lower likelihood of meeting all QMs included Black race (adjusted odds ratio [aOR], 0.744; 95% CI, 0.652-0.848), higher area deprivation index score (eg, quartile 5 vs 1; aOR, 0.747; 95% CI, 0.647-0.863), and increased distance to hospital (eg, quartile 5 vs 1; aOR, 0.700; 95% CI, 0.605-0.811). Adherence to all QMs was associated with significantly lower likelihood of postoperative mortality (aOR, 0.623; 95% CI, 0.433-0.896) and improved overall survival (adjusted HR, 0.897; 95% CI, 0.844-0.954). Inadequate access to preoperative care is associated with worse short- and long-term outcomes in clinical stage I NSCLC. Future Veterans Health Administration policy measures should focus on providing more equitable guideline-concordant care to veterans. [Display omitted] [ABSTRACT FROM AUTHOR]