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.

A Novel Probiotic-Based Oral Vaccine against SARS-CoV-2 Omicron Variant B.1.1.529.

COVID-19 pandemic, caused by the SARS-CoV-2 virus, is still affecting the entire world via the rapid emergence of new contagious variants. Vaccination remains the most effective prevention strategy for viral infection, yet not all countries have sufficient access to vaccines due to limitations in manufacturing and transportation. Thus, there is an urgent need to develop an easy-to-use, safe, and low-cost vaccination approach. Genetically modified microorganisms, especially probiotics, are now commonly recognized as attractive vehicles for delivering bioactive molecules via oral and mucosal routes. In this study, Lactobacillus casei has been selected as the oral vaccine candidate based on its' natural immunoadjuvant properties and the ability to resist acidic gastric environment, to express antigens of SARS-CoV-2 Omicron variant B.1.1.529 with B-cell and T-cell epitopes. This newly developed vaccine, OMGVac, was shown to elicit a robust IgG systemic immune response against the spike protein of Omicron variant B.1.1.529 in Golden Syrian hamsters. No adverse effects were found throughout this study, and the overall safety was evaluated in terms of physiological and histopathological examinations of different organs harvested. In addition, this study illustrated the use of the recombinant probiotic as a live delivery vector in the initiation of systemic immunity, which shed light on the future development of next-generation vaccines to combat emerging infectious diseases.

Efficacy of mesh coverage in surgical bullectomy for primary spontaneous pneumothorax: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Thoracic surgeons are now adopting a new method of using a mesh covering to reduce recurrence in surgical pleurodesis for pneumothorax. We aimed to review the literature and compare the outcomes of using mesh covering as an additional procedure during surgical pleurodesis. METHODS: A comprehensive search was performed from inception to October 2022 on PubMed, Embase, Cochrane and Scopus. Randomised controlled trials (RCTs) and observational cohort studies (OCSs) comparing the use of mesh coverage, and different materials were included. Data were extracted to compare recurrence and other outcomes using a random effect model. RESULTS: 23 studies consisting of 2 RCTs and 21 OCSs totalling 5092 patients were included. Patients with a mesh had a significantly lower recurrence (OR = 0.22, 95% CI 0.12-0.42, p < 0.0001) and a shorter duration of chest tube drainage (SMD = -0.74 days, 95% CI -0.28 to -1.20, p < 0.0001) but no significant difference in the length of operation. The use of polyglycolic acid (PGA) and vicryl mesh was associated with a significantly shorter duration of chest tube drainage [(PGA, SMD = 0.83 days, 95% CI 0.14-1.52, p < 0.0001), (vicryl, SMD = 1.06 days, 95% CI 0.71-2.82, p = 0.0005)]. They also had a shorter post-operative length of stay than oxidized regenerative cellulose (ORC) but this was not statistically significant. CONCLUSION: The use of a mesh material reduced the incidence of post-operative air leaks in the short term and the recurrence rate in the long term. Some mesh materials such as PGA and vicryl performed better than other materials.

Intestinal bile acids provide a surmountable barrier against C. difficile TcdB-induced disease pathogenesis.

Intestinal bile acids play an essential role in the Clostridioides difficile lifecycle having been shown in vitro to modulate various aspects of pathogenesis, including spore germination, vegetative growth, and more recently the action of the primary virulence determinant, TcdB. Here, we investigated whether physiological levels of the total pool of intestinal bile acids in mice and humans protect against TcdB action. Small molecules extracted from the lumenal contents of the small intestine, cecum, colon, and feces were found to inhibit TcdB in accordance with the differential amounts of total bile acids in each compartment. Extracts from antibiotic-treated and germ-free mice, despite harboring dramatically altered bile acid profiles, unexpectedly also prevented TcdB-induced cell rounding to similar extents. We show that protection, however, is surmountable and can be overcome at higher doses of TcdB-typical to those seen during severe C. difficile infection-suggesting that the protective properties of intestinal bile acids are operant primarily under low to moderate toxin levels. Taken together, these findings demonstrate a role for intestinal bile acids in attenuating virulence, provide insights into asymptomatic carriage of toxigenic C. difficile, and inform strategies to manipulate bile acid levels for therapeutic benefit.

Small Molecule Inhibition of an Exopolysaccharide Modification Enzyme is a Viable Strategy To Block Pseudomonas aeruginosa Pel Biofilm Formation.

Biosynthesis of the Pel exopolysaccharide in Pseudomonas aeruginosa requires all seven genes of the pelABCDEFG operon. The periplasmic modification enzyme PelA contains a C-terminal deacetylase domain that is necessary for Pel-dependent biofilm formation. Herein, we show that extracellular Pel is not produced by a P. aeruginosa PelA deacetylase mutant. This positions PelA deacetylase activity as an attractive target to prevent Pel-dependent biofilm formation. Using a high-throughput screen (n = 69,360), we identified 56 compounds that potentially inhibit PelA esterase activity, the first enzymatic step in the deacetylase reaction. A secondary biofilm inhibition assay identified methyl 2-(2-pyridinylmethylene) hydrazinecarbodithioate (SK-017154-O) as a specific Pel-dependent biofilm inhibitor. Structure-activity relationship studies identified the thiocarbazate as a necessary functional group and that the pyridyl ring could be replaced with a phenyl substituent (compound 1). Both SK-017154-O and compound 1 inhibit Pel-dependent biofilm formation in Bacillus cereus ATCC 10987, which has a predicted extracellular PelA deacetylase in its pel operon. Michaelis-Menten kinetics determined SK-017154-O to be a noncompetitive inhibitor of PelA, while compound 1 did not directly inhibit PelA esterase activity. Cytotoxicity assays using human lung fibroblast cells showed that compound 1 is less cytotoxic than SK-017154-O. This work provides proof of concept that biofilm exopolysaccharide modification enzymes are important for biofilm formation and can serve as useful antibiofilm targets. IMPORTANCE Present in more than 500 diverse Gram-negative and 900 Gram-positive organisms, the Pel polysaccharide is one of the most phylogenetically widespread biofilm matrix determinants found to date. Partial de-N-acetylation of this α-1,4 linked N-acetylgalactosamine polymer by the carbohydrate modification enzyme PelA is required for Pel-dependent biofilm formation in Pseudomonas aeruginosa and Bacillus cereus. Given this and our observation that extracellular Pel is not produced by a P. aeruginosa PelA deactylase mutant, we developed an enzyme-based high-throughput screen and identified methyl 2-(2-pyridinylmethylene) hydrazinecarbodithioate (SK-017154-O) and its phenyl derivative as specific Pel-dependent biofilm inhibitors. Michaelis-Menten kinetics revealed SK-017154-O is a noncompetitive inhibitor and that its noncytotoxic, phenyl derivative does not directly inhibit P. aeruginosa PelA esterase activity. We provide proof of concept that exopolysaccharide modification enzymes can be targeted with small molecule inhibitors to block Pel-dependent biofilm development in both Gram-negative and Gram-positive bacteria.

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.

Tauroursodeoxycholic Acid Inhibits Clostridioides difficile Toxin-Induced Apoptosis.

C. difficile infection (CDI) is a highly inflammatory disease mediated by the production of two large toxins that weaken the intestinal epithelium and cause extensive colonic tissue damage. Antibiotic alternative therapies for CDI are urgently needed as current antibiotic regimens prolong the perturbation of the microbiota and lead to high disease recurrence rates. Inflammation is more closely correlated with CDI severity than bacterial burden, thus therapies that target the host response represent a promising yet unexplored strategy for treating CDI. Intestinal bile acids are key regulators of gut physiology that exert cytoprotective roles in cellular stress, inflammation, and barrier integrity, yet the dynamics between bile acids and host cellular processes during CDI have not been investigated. Here we show that several bile acids are protective against apoptosis caused by C. difficile toxins in Caco-2 cells and that protection is dependent on conjugation of bile acids. Out of 20 tested bile acids, taurine conjugated ursodeoxycholic acid (TUDCA) was the most potent inhibitor, yet unconjugated UDCA did not alter toxin-induced apoptosis. TUDCA treatment decreased expression of genes in lysosome associated and cytokine signaling pathways. TUDCA did not affect C. difficile growth or toxin activity in vitro whereas UDCA significantly reduced toxin activity in a Vero cell cytotoxicity assay and decreased tcdA gene expression. These results demonstrate that bile acid conjugation can have profound effects on C. difficile as well as the host and that conjugated and unconjugated bile acids may exert different therapeutic mechanisms against CDI.

Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells.

An essential step in the infection life cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the proteolytic activation of the viral spike (S) protein, which enables membrane fusion and entry into the host cell. Two distinct classes of host proteases have been implicated in the S protein activation step: cell-surface serine proteases, such as the cell-surface transmembrane protease, serine 2 (TMPRSS2), and endosomal cathepsins, leading to entry through either the cell-surface route or the endosomal route, respectively. In cells expressing TMPRSS2, inhibiting endosomal proteases using nonspecific cathepsin inhibitors such as E64d or lysosomotropic compounds such as hydroxychloroquine fails to prevent viral entry, suggesting that the endosomal route of entry is unimportant; however, mechanism-based toxicities and poor efficacy of these compounds confound our understanding of the importance of the endosomal route of entry. Here, to identify better pharmacological agents to elucidate the role of the endosomal route of entry, we profiled a panel of molecules identified through a high-throughput screen that inhibit endosomal pH and/or maturation through different mechanisms. Among the three distinct classes of inhibitors, we found that inhibiting vacuolar-ATPase using the macrolide bafilomycin A1 was the only agent able to potently block viral entry without associated cellular toxicity. Using both pseudotyped and authentic virus, we showed that bafilomycin A1 inhibits SARS-CoV-2 infection both in the absence and presence of TMPRSS2. Moreover, synergy was observed upon combining bafilomycin A1 with Camostat, a TMPRSS2 inhibitor, in neutralizing SARS-CoV-2 entry into TMPRSS2-expressing cells. Overall, this study highlights the importance of the endosomal route of entry for SARS-CoV-2 and provides a rationale for the generation of successful intervention strategies against this virus that combine inhibitors of both entry pathways.

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.

Partial Versus Complete Thymectomy in Non-Myasthenic Patients With Thymoma: A Systematic Review and Meta-Analysis of Clinical Outcomes.

OBJECTIVE: The optimal extent of surgical resection for non-myasthenic patients with thymoma is controversial. The objective of this meta-analysis was to compare complete to partial thymectomy in non-myasthenic patients for oncological and postoperative clinical outcomes. METHODS: We performed a PubMed and EMBASE search (from inception to January 2020) for English-language studies directly comparing partial thymectomy (thymomectomy) to complete thymectomy for thymoma resection. Clinical endpoints studied included overall and disease-free survival, Masaoka and World Health Organization staging, adjuvant therapy, postoperative complications, postoperative drainage, length of hospital stay, thymoma-related deaths, postresection development of myasthenia gravis, incomplete resection, and recurrence. Random effects meta-analyses across all clinical endpoints was done. RESULTS: There was no statistically significant difference between the two approaches with regard to recurrence (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.78-1.92), completeness of resection (OR, 1.17; 95% CI, 0.66-2.10), adjuvant therapy (OR, 0.71; 95% CI, 0.40-1.26), or thymoma-related deaths (OR, 0.76; 95% CI, 0.12-4.66). There was a statistically significant decrease in postoperative complications (OR, 0.61; 95% CI, 0.39-0.97), drainage (mean difference [MD], -0.99; 95% CI, -1.98 to -0.01), and length of hospital length (MD, -1.88; 95% CI, -3.39 to -0.36) with partial thymectomy. CONCLUSIONS: The evidence appeared to suggest that partial thymectomy is oncologically equivalent to complete thymectomy for non-myasthenic patients with early-stage thymoma. There is an additional advantage of reduced postoperative complications and decreased length of hospital stay with partial thymectomy.

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.

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.

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.