Healthcare sustainability in cardiothoracic surgery.

BACKGROUND: Climate change is the greatest threat to human health. Cardiothoracic patients suffer direct consequences from poor environmental health and we have a vested interest to address this in our practice. As leaders of complex high-end surgery, we are uniquely positioned to effect practical and immediate changes to significantly pare down emissions within the operating theatre, outside the operating theatre and beyond the confines of the hospital. METHODS: We aim to spotlight this pressing issue, take stock of our current efforts, and encourage fellow specialists to drive this agenda. RESULTS: Sustainability in healthcare needs to be formalized as part of the core curriculum in surgical training and awareness generated via carbon audits and life cycle analyses. Practical actions such as reducing unnecessary equipment usage, choosing reusable equipment over single use disposables, judicious use of investigations rooted in clinical reasoning and sharing of resources across services and health systems help reduce the carbon output of our specialty. CONCLUSION: The 'Triple Bottom Line' serves as a good template to calibrate efforts that balance quality against environmental costs. More can be done to advocate for and find solutions for sustainable healthcare with cardiothoracic surgery.

Lung erosion following adjuvant immunotherapy with pembrolizumab: a case report.

BACKGROUND: Pembrolizumab as immunotherapy is increasingly used in adjuvant, neoadjuvant, and standalone therapy and has been described as safe. We share an experience of lung erosion post-thoracic surgery with the use of adjuvant pembrolizumab. CASE PRESENTATION: A 65-year-old Chinese gentleman with metastatic renal cell carcinoma underwent lung metastasis resection and presented with delayed onset pneumothorax while on adjuvant pembrolizumab. Failure of conservative management warranted repeat surgical intervention, and intraoperative findings showed erosion of staple lines possibly caused by poor healing associated with pembrolizumab. CONCLUSION: Adjuvant pembrolizumab may impair wound healing, including stapler line healing. Presentation of delayed pneumothorax in a post-surgical patient undergoing immunotherapy should warrant early surgical intervention.

Quality of life with minimally invasive repair of pectus excavatum: a systematic review and meta-analysis.

Background: Minimally invasive repair of pectus excavatum (MIRPE) is a popular method for surgical correction of PE, and its impact on quality of life is a growing area of interest. We performed a systematic review and meta-analysis to evaluate the impact of MIRPE on the quality of life of patients. Methods: This study was registered with PROSPERO under reference number CRD42020222061. A literature search of PubMed, Cochrane Library, EMBASE and Scopus was conducted from the date of inception till November 23, 2020. We included studies which administered one or more questionnaires on patients up to 60 years old, parents or both, to assess the quality of life before and after MIRPE. Studies not written in English, abstracts, articles without primary data, reviews and studies which combined data on PE and other deformities were excluded. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions and the Cochrane risk of bias tool. A random-effects meta-analysis was performed to obtain mean differences for key themes of quality of life before and after MIRPE. Responses from the same questionnaires, as well as common themes across different questionnaires, were compared. Results: Of the 20 studies identified for systematic review, 7 studies that reported the responses of 478 patients were included in the meta-analysis. Patients who underwent MIRPE experienced an increased self-esteem [standardized mean difference (SMD): 1.38, 95% confidence interval (CI): 0.95 to 1.81, P<0.00001] and a smaller degree of chest interference with their social activities (SMD: 0.84, 95% CI: 0.60 to 1.08, P<0.00001). These findings were consistent even after the implanted bar was removed. Conclusions: MIRPE may be associated with a better quality of life for patients with PE as self-esteem and extent of chest interference with social activities are improved after the procedure. The key limitations of this study are the lack of high-quality evidence due to paucity of randomized trials, and the significant heterogeneity in reported outcomes due to variations in the questionnaires and timepoints of administration.

Novel Nuss Bar Fixation Using ZipFix for Pectus Excavatum.

BACKGROUND: Bar displacement is one of the most serious complications following the Nuss procedure for pectus excavatum repair. This paper reports a novel method of bar fixation using ZipFix, a biocompatible cable-tie implant, and shares a series of patients and outcomes. METHODS: This paper describes the ZipFix stabilisation method and presents a case series of 20 patients with pectus excavatum who underwent the Nuss procedure and ZipFix stabilisation between July 2015 and September 2020. RESULTS: A total of 34 ZipFixes were implanted in 20 patients. Six (6) patients had one ZipFix placed and 14 patients had two ZipFixes implanted: 13 were bilateral and one patient had two ZipFixes placed on the right. There was one incidence of asymptomatic posterior superior displacement of the right bar. Two (2) patients had wound infections and one patient had a previously placed bar adjusted and secured with a ZipFix. All patients had full correction of their chest wall deformity with no recurrence. CONCLUSIONS: This case series shows that the use of ZipFix for Nuss bar fixation is feasible using this technique.

From Pandemic to Endemic-Redefining Excellence in Thoracic Surgery Service Delivery.

Covid-19 has touched all corners of the globe and impacted our lives in more ways than one. Thoracic surgeons are frontliners impacted in both our professional and personal capacities. In this commentary we discuss the impact that Covid-19 has had on thoracic surgery as a practice highlighting the discrepant impact upon developed and developing countries, the state of affairs of the "new normal" that we live in and the challenges ahead as we transition from pandemic living to endemic living alongside Covid-19. We need to evolve as the virus does and keep abreast of the latest developments to continue providing excellent care to our patients. While the challenges brought about by the Covid-19 pandemic are unprecedented in this generation, it can bring forth tremendous opportunities for us to redefine excellence in thoracic surgery service delivery in this endemic times.

Bronchial rupture following endobronchial blocker placement: a case report of a rare, unfortunate complication.

BACKGROUND: Lung separation may be achieved through the use of double lumen tubes or endobronchial blockers. The use of lung separation techniques carries the risk of airway injuries which range from minor complications like postoperative hoarseness and sore throat to rare and potentially devastating tracheobronchial mucosal injuries like bronchus perforation or rupture. With few case reports to date, bronchial rupture with the use of endobronchial blockers is indeed an overlooked complication. CASE PRESENTATION: A 78-year-old male patient with a left upper lobe lung adenocarcinoma underwent a left upper lobectomy with a Fuji Uniblocker® as the lung separation device. Despite an atraumatic insertion and endobronchial blocker balloon volume within manufacturer specifications, an intraoperative air leak developed, and the patient was found to have sustained a left mainstem bronchus rupture which was successfully repaired and the patient extubated uneventfully. Unfortunately, the patient passed on in-hospital from sepsis and other complications. CONCLUSION: Bronchial rupture is a serious complication of endobronchial blocker use that can carry significant morbidity, and due care should be exercised in its use and placement. Bronchoscopy should be used during insertion, and the volume and pressure of the balloon kept to the minimum required to prevent air leak. Bronchial injury should be considered as a differential in the presence of an unexplained air leak.

Incorporation of an intercostal catheter into a multimodal analgesic strategy for uniportal video-assisted thoracoscopic surgery: a feasibility study.

BACKGROUND: Well-controlled postoperative pain is essential for early recovery after uniportal video-assisted thoracoscopic surgery (UVATS). Conventional analgesia like opioids and thoracic epidural anaesthesia have been associated with hypotension and urinary retention. Intercostal catheters are a regional analgesic alternative that can be inserted during UVATS to avoid these adverse effects. This feasibility study aims to evaluate the postoperative pain scores and analgesic requirements with incorporation of an intercostal catheter into a multimodal analgesic strategy for UVATS. METHODS: In this observational study, 26 consecutive patients who underwent UVATS were administered a multilevel intercostal block and oral paracetamol. All of these patients received 0.2% ropivacaine continuously at 4 ml/h via an intercostal catheter at the level of the incision. Rescue analgesia including etoricoxib, gabapentin and opioids were prescribed using a pain ladder approach. Postoperative pain scores and analgesic usage were assessed. The secondary outcomes were postoperative complications, days to ambulation and length of stay. RESULTS: No technical difficulties were encountered during placement of the intercostal catheter. There was only one case of peri-catheter leakage. Mean pain score was 0.31 (range 0-2) on post-operative day 1 and was 0.00 by post-operative day 5. 16 patients (61.6%) required only oral rescue analgesia. The number of patients who required rescue non-opioids only increased from 1 in the first 7 months to 8 in the next 7 months. There were no cases of hypotension or urinary retention. Median time to ambulation was 1 day (range 1-2). Mean post-operative length of stay was 4.17 ± 2.50 days. CONCLUSIONS: Incorporation of an intercostal catheter into a multimodal analgesia strategy for UVATS is feasible and may provide adequate pain control with decreased opioid usage.

Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

Antifibrinolytics reduces blood loss in thoracic surgery: a systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review is to evaluate the efficacy of antifibrinolytics in non-cardiac thoracic surgery. METHODS: We searched for all randomized controlled trials on this topic. A set of strict inclusion and exclusion criteria was developed. Six studies were meta-analysed together then in subgroups of topical tranexamic acid and intravenous aprotinin. We compared postoperative chest drain output, transfusions requirements and duration of hospital stay where available to determine the efficacy of topical tranexamic acid or intravenous aprotinin in reducing blood loss. RESULTS: The use of antifibrinolytics reduces 24-h chest drain output (-290.21 mL [-524.75, -55.66], P = 0.02, I2  = 98%), red blood cell transfusion requirements (-1.27 units [-2.24, -0.30], P = 0.01, I2  = 100%) and shortened duration of hospital stay (-1.81 days [-3.25, -0.36], P = 0.01, I2  = 96%). The subgroup analysis also supported this trend. CONCLUSION: We conclude that the use of antifibrinolytics appears to reduce postoperative blood loss by reducing chest drain output, transfusion requirements and length of stay after thoracic surgery.

Rescue extracorporeal membrane oxygenation for massive anterior mediastinal masses.

The management of massive anterior mediastinal masses (AMM) is challenging. With the burgeoning role of extracorporeal membrane oxygenation support (ECMO) beyond the confines of salvage therapy, more trained clinicians are adopting it as a bridge for high-risk procedures or situations where temporary respiratory or cardiac support is required. We report our experience with using ECMO in the management of massive AMM in this case series of three patients sharing their clinical details and the lessons learned from them.

Organization of thoracic surgical services during the COVID pandemic.

INTRODUCTION: COVID-19 presented an unprecedented challenge for healthcare workers and systems around the world. Healthcare systems have adapted differently in terms of pandemic planning of regular services, adopting infection control measures and prioritising essential hospital services in the context of a burgeoning COVID-19 patient load and inevitable surge. METHODS: We performed a review on current evidence and share our practices at a teaching hospital in Singapore. RESULTS: We outline principles and make recommendations for continuity of delivering essential thoracic surgical services during this current outbreak. CONCLUSIONS: The maintenance and provision of thoracic surgery services in this context requires good preplanning and vigilance to infection control measures across all levels.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.

Eomes Expression Defines Group 1 Innate Lymphoid Cells During Metastasis in Human and Mouse.

Recent studies have attempted to uncover the role of Group 1 Innate lymphoid cells (ILCs) in multiple physiological contexts, including cancer. However, the definition and precise contribution of Group 1 ILCs (constituting ILC1 and NK subsets) to metastasis is unclear due to the lack of well-defined cell markers. Here, we first identified ILC1 and NK cells in NSCLC patient blood and differentiated them based on the expression of transcription factors, T-bet and Eomes. Interestingly, Eomes downregulation in the peripheral blood NK cells of NSCLC patients positively correlated with disease progression. Additionally, we noted higher Eomes expression in NK cells (T-bet+Eomeshi) compared to ILC1s (T-bet+Eomeslo). We asked whether the decrease in Eomes was associated with the conversion of NK cells into ILC1 using Eomes as a reliable marker to differentiate ILC1s from NK cells. Utilizing a murine model of experimental metastasis, we observed an association between increase in metastasis and Eomes downregulation in NKp46+NK1.1+ Group 1 ILCs, which was consistent to that of human NSCLC samples. Further confirmation of this trend was achieved by flow cytometry, which identified tissue-specific Eomeslo ILC1-like and Eomeshi NK-like subsets in the murine metastatic lung based on cell surface markers and adoptive transfer experiments. Next, functional characterization of these cell subsets showed reduced cytotoxicity and IFNγ production in Eomeslo ILC1s compared to Eomeshi cells, suggesting that lower Eomes levels are associated with poor cancer immunosurveillance by Group 1 ILCs. These findings provide novel insights into the regulation of Group 1 ILC subsets during metastasis, through the use of Eomes as a reliable marker to differentiate between NK and ILC1s.

pHLuc, a Ratiometric Luminescent Reporter for in vivo Monitoring of Tumor Acidosis.

Even under normoxia, cancer cells exhibit increased glucose uptake and glycolysis, an occurrence known as the Warburg effect. This altered metabolism results in increased lactic acid production, leading to extracellular acidosis and contributing to metastasis and chemoresistance. Current pH imaging methods are invasive, costly, or require long acquisition times, and may not be suitable for high-throughput pre-clinical small animal studies. Here, we present a ratiometric pH-sensitive bioluminescence reporter called pHLuc for in vivo monitoring of tumor acidosis. pHLuc consists of a pH-sensitive GFP (superecliptic pHluorin or SEP), a pH-stable OFP (Antares), and Nanoluc luciferase. The resulting reporter produces a pH-responsive green 510nm emission (from SEP) and a pH-insensitive red-orange 580nm emission (from Antares). The ratiometric readout (R580 / 510) is indicative of changes in extracellular pH (pHe). In vivo proof-of-concept experiments with NSG mice model bearing human synovial sarcoma SW982 xenografts that stably express the pHLuc reporter suggest that the level of acidosis varies across the tumor. Altogether, we demonstrate the diagnostic value of pHLuc as a bioluminescent reporter for pH variations across the tumor microenvironment. The pHLuc reporter plasmids constructed in this work are available from Addgene.

Novel AU-rich proximal UTR sequences (APS) enhance CXCL8 synthesis upon the induction of rpS6 phosphorylation.

The role of ribosomal protein S6 (rpS6) phosphorylation in mRNA translation remains poorly understood. Here, we reveal a potential role in modulating the translation rate of chemokine (C-X-C motif) ligand 8 (CXCL8 or Interleukin 8, IL8). We observed that more CXCL8 protein was being secreted from less CXCL8 mRNA in primary macrophages and macrophage-like HL-60 cells relative to other cell types. This correlated with an increase in CXCL8 polyribosome association, suggesting an increase in the rate of CXCL8 translation in macrophages. The cell type-specific expression levels were replicated by a CXCL8- UTR-reporter (Nanoluc reporter flanked by the 5' and 3' UTR of CXCL8). Mutations of the CXCL8-UTR-reporter revealed that cell type-specific expression required: 1) a 3' UTR of at least three hundred bases; and 2) an AU base content that exceeds fifty percent in the first hundred bases of the 3' UTR immediately after the stop codon, which we dub AU-rich proximal UTR sequences (APS). The 5' UTR of CXCL8 enhanced expression at the protein level and conferred cell type-specific expression when paired with a 3' UTR. A search for other APS-positive mRNAs uncovered TNF alpha induced protein 6 (TNFAIP6), another mRNA that was translationally upregulated in macrophages. The elevated translation of APS-positive mRNAs in macrophages coincided with elevated rpS6 S235/236 phosphorylation. Both were attenuated by the ERK1/2 signaling inhibitors, U0126 and AZD6244. In A549 cells, rpS6 S235/236 phosphorylation was induced by TAK1, Akt or PKA signaling. This enhanced the translation of the CXCL8-UTR-reporters. Thus, we propose that the induction of rpS6 S235/236 phosphorylation enhances the translation of mRNAs that contain APS motifs, such as CXCL8 and TNFAIP6. This may contribute to the role of macrophages as the primary producer of CXCL8, a cytokine that is essential for immune cell recruitment and activation.