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Background: The utilization of three-dimensional printing has grown rapidly within the field of surgery over recent years. Within the subspecialty of colorectal surgery, the technology has been used to create personalized anatomical models for preoperative planning, models for surgical training, and occasionally customized implantable devices and surgical instruments. We aim to provide a systematic review of the current literature discussing clinical applications of three-dimensional printing in colorectal surgery., Methods: Full-text studies published in English which described the application of 3D printing in pre-surgical planning, advanced surgical planning, and patient education within the field of colorectal surgery were included. Exclusion criteria were duplicate articles, review papers, studies exclusively dealing with surgical training and/or education, studies which used only virtual models, and studies which described colorectal cancer only as it pertained to other organs., Results: Eighteen studies were included in this review. There were two randomized controlled trials, one retrospective outcomes study, five case reports/series, one animal model, and nine technical notes/feasibility studies. There were three studies on advanced surgical planning/device manufacturing, six on pre-surgical planning, two on pelvic anatomy modeling, eight on various types of anatomy modeling, and one on patient education., Conclusions: While more studies with a higher level of evidence are needed, the findings of this review suggest many promising applications of three-dimensional printing within the field of colorectal surgery with the potential to improve patient outcomes and experiences., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The optimal timing of surgical repair for infants with complete atrioventricular canal defect remains controversial, as there are risks to both early and late repair. We address this debate by investigating the association of various risk factors, including age and weight at surgery, markers of failure to thrive, and pulmonary vascular disease, with postoperative length of stay following complete atrioventricular canal repair., Methods: Infants who underwent repair of complete atrioventricular canal were identified from our institutional Society of Thoracic Surgeons Congenital Heart Surgery Database. Additional clinical data were collected from the electronic medical record. Descriptive statistics were computed. Associations between postoperative length of stay and covariates of interest were evaluated using linear regression with bootstrap aggregation., Results: From 2001 to 2020, 150 infants underwent isolated complete atrioventricular canal repair at our institution. Pre-operative failure to thrive and evidence of pulmonary disease were common. Surgical mortality was 2%. In univariable analysis, neither weight nor age at surgery were associated with mortality, postoperative length of stay, duration of mechanical ventilation, or post-operative severe valvular regurgitation. In multivariable analysis of demographic and preoperative clinical factors using bootstrap aggregation, increased postoperative length of stay was only significantly associated with previous pulmonary artery banding (33.9 day increase, p = 0.03) and preoperative use of supplemental oxygen (19.9 day increase, p = 0.03)., Conclusions: Our analysis shows that previous pulmonary artery banding and preoperative use of supplemental oxygen were associated with increased postoperative length of stay after complete atrioventricular canal repair, whereas age and weight were not. These findings suggest operation prior to the onset of pulmonary involvement may be more important than reaching age or weight thresholds.

Introduction: Tissue plasminogen activator (tPA), commonly used for treatment of acute ischemic stroke, is associated with life-threatening bleeding intracranially as well as surrounding the airway., Case Report: A 78-year-old year old male who presented with stroke symptoms and after tPA administration developed a retropharyngeal hematoma requiring intubation and surgical intervention., Conclusion: Numerous threats to the patient's airway can develop after tPA administration. While angioedema is the most common cause, it is important to be prepared for other causes related to hemorrhage.

Lung organogenesis requires precise timing and coordination to effect spatial organization and function of the parenchymal cells. To provide a systematic broad-based view of the mechanisms governing the dynamic alterations in parenchymal cells over crucial periods of development, we performed a single-cell RNA-sequencing time-series yielding 102,571 epithelial, endothelial and mesenchymal cells across nine time points from embryonic day 12 to postnatal day 14 in mice. Combining computational fate-likelihood prediction with RNA in situ hybridization and immunofluorescence, we explore lineage relationships during the saccular to alveolar stage transition. The utility of this publicly searchable atlas resource (www.sucrelab.org/lungcells) is exemplified by discoveries of the complexity of type 1 pneumocyte function and characterization of mesenchymal Wnt expression patterns during the saccular and alveolar stages - wherein major expansion of the gas-exchange surface occurs. We provide an integrated view of cellular dynamics in epithelial, endothelial and mesenchymal cell populations during lung organogenesis., Competing Interests: Competing interests J.A.K. has received advisory board fees from Boehringer Ingelheim and Janssen Therapeutics, grants from Boehringer Ingelheim and Bristol-Myers-Squibb and research contracts with Genentech. T.S.B. has received advisory board fees from Boehringer Ingelheim, Orinove, GRI Bio, Morphic and Novelstar, and has research contracts with Genentech and Celgene., (© 2021. Published by The Company of Biologists Ltd.)

Objective: The benefits of minimally invasive adult cardiac surgery are well established. Nevertheless, minimally invasive congenital cardiac procedures, even for adult patients, are uncommon. In 2018, we started repairing anomalous aortic origin of a coronary artery (AAOCA) through a 5 cm anterior minithoracotomy when possible to improve cosmesis and avoid sternal precautions. We hypothesized this approach was safe and reliable., Methods: A 5 cm incision was made in the right second intercostal space. The incision was carried down to the pericardium while preserving the internal mammary artery. With the pericardium in view, the second and third ribs were disarticulated. Central cardiopulmonary bypass was established, and the repair was carried out based on the patient's anatomy. The technique was modified to a left anterior minithoracotomy for 1 patient who required pulmonary artery translocation. At any point, if the dissection or repair was not progressing appropriately, the minimally invasive exposure was converted to a partial or traditional median sternotomy., Results: Between June 2018 and June 2019, 11 patients underwent minimally invasive anomalous coronary repair. Four patients (3 with body mass index >30) were converted to traditional sternotomy due to poor visualization. Postoperatively, 1 patient required coronary artery bypass after 335 days, due to extensive collaterals and stable angina. Otherwise, at a median follow-up of 437 days (IQR 340 to 480), patients had resumed baseline activity without recurrent symptoms., Conclusions: Minimally invasive AAOCA repair may be appealing, although surgeons should be cautious given the high conversion rate.

Background: Cellular diversity of the lung endothelium has not been systematically characterized in humans. We provide a reference atlas of human lung endothelial cells (ECs) to facilitate a better understanding of the phenotypic diversity and composition of cells comprising the lung endothelium., Methods: We reprocessed human control single-cell RNA sequencing (scRNAseq) data from 6 datasets. EC populations were characterized through iterative clustering with subsequent differential expression analysis. Marker genes were validated by fluorescent microscopy and in situ hybridization. scRNAseq of primary lung ECs cultured in vitro was performed. The signaling network between different lung cell types was studied. For cross-species analysis or disease relevance, we applied the same methods to scRNAseq data obtained from mouse lungs or from human lungs with pulmonary hypertension., Results: Six lung scRNAseq datasets were reanalyzed and annotated to identify >15 000 vascular EC cells from 73 individuals. Differential expression analysis of EC revealed signatures corresponding to endothelial lineage, including panendothelial, panvascular, and subpopulation-specific marker gene sets. Beyond the broad cellular categories of lymphatic, capillary, arterial, and venous ECs, we found previously indistinguishable subpopulations; among venous EC, we identified 2 previously indistinguishable populations: pulmonary-venous ECs (COL15A1 neg ) localized to the lung parenchyma and systemic-venous ECs (COL15A1 pos ) localized to the airways and the visceral pleura; among capillary ECs, we confirmed their subclassification into recently discovered aerocytes characterized by EDNRB , SOSTDC1 , and TBX2 and general capillary EC. We confirmed that all 6 endothelial cell types, including the systemic-venous ECs and aerocytes, are present in mice and identified endothelial marker genes conserved in humans and mice. Ligand-receptor connectome analysis revealed important homeostatic crosstalk of EC with other lung resident cell types. scRNAseq of commercially available primary lung ECs demonstrated a loss of their native lung phenotype in culture. scRNAseq revealed that endothelial diversity is maintained in pulmonary hypertension. Our article is accompanied by an online data mining tool (www.LungEndothelialCellAtlas.com)., Conclusions: Our integrated analysis provides a comprehensive and well-crafted reference atlas of ECs in the normal lung and confirms and describes in detail previously unrecognized endothelial populations across a large number of humans and mice.

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection., (© 2021. The Author(s).)

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.

Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5 - / KRT17 + pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The right anterior mini-incision has emerged as an effective minimally invasive approach for adult aortic root and valve operations. However, adoption of minimally invasive techniques has been limited in congenital heart surgery. We report a case of anomalous aortic origin of the right coronary artery repair performed through this approach. Following successful right coronary artery unroofing, the patient had an uncomplicated postoperative hospitalization.

Although the lung is the most common metastatic site for cancer cells, biologic mechanisms regulating lung metastasis are not fully understood. Using heterotopic and intravenous injection models of lung metastasis in mice, we found that IL5, a cytokine involved in allergic and infectious diseases, facilitates metastatic colonization through recruitment of sentinel eosinophils and regulation of other inflammatory/immune cells in the microenvironment of the distal lung. Genetic IL5 deficiency offered marked protection of the lungs from metastasis of different types of tumor cells, including lung cancer, melanoma, and colon cancer. IL5 neutralization protected subjects from metastasis, whereas IL5 reconstitution or adoptive transfer of eosinophils into IL5-deficient mice exerted prometastatic effects. However, IL5 deficiency did not affect the growth of the primary tumor or the size of metastatic lesions. Mechanistic investigations revealed that eosinophils produce CCL22, which recruits regulatory T cells to the lungs. During early stages of metastasis, Treg created a protumorigenic microenvironment, potentially by suppressing IFNγ-producing natural killer cells and M1-polarized macrophages. Together, our results establish a network of allergic inflammatory circuitry that can be co-opted by metastatic cancer cells to facilitate lung colonization, suggesting interventions to target this pathway may offer therapeutic benefits to prevent or treat lung metastasis., (©2015 American Association for Cancer Research.)