Publications by authors named "Kalvin Lung"

9 Publications

  • Page 1 of 1

Lung donation following SARS-CoV-2 infection.

Am J Transplant 2021 Jul 31. Epub 2021 Jul 31.

Division of Thoracic Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and "efficacy" of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.
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http://dx.doi.org/10.1111/ajt.16777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441925PMC
July 2021

Straight Curves: Incidental Diagnosis of Pneumothorax on Transesophageal Echocardiography.

Am J Respir Crit Care Med 2021 Apr 28. Epub 2021 Apr 28.

University of Toronto, 7938, Toronto, Ontario, Canada;

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http://dx.doi.org/10.1164/rccm.202011-4274IMDOI Listing
April 2021

Commentary: Bruised donor lungs-they may not be pretty, but they will still work.

J Thorac Cardiovasc Surg 2021 Jan 23. Epub 2021 Jan 23.

Toronto Lung Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.12.045DOI Listing
January 2021

Paraconduit Hernia in the Era of Minimally Invasive Esophagectomy: Underdiagnosed?

Ann Thorac Surg 2021 06 5;111(6):1812-1819. Epub 2020 Oct 5.

Division of Thoracic Surgery, Toronto General Hospital, University Hospital Network, Toronto, Ontario, Canada. Electronic address:

Background: There is a need to compare the proportions, risk factors, and natural histories of postesophagectomy paraconduit hernias in minimally invasive and open esophagectomies.

Methods: This is a single-center, retrospective cohort study of esophageal cancer surgery performed between 2007 and 2017. Postesophagectomy paraconduit hernias were identified on cross-sectional imaging. Patient charts were reviewed to describe the management and natural history.

Results: Between 2007 and 2017, 391 esophagectomies were performed. After exclusions, 347 patients remained, 135 of whom were total minimally invasive esophagectomies (MIEs) (39%). Postoperative paraconduit hernias developed in 10% of patients. Median time to diagnosis was 258 days. Of 135 MIEs, 20 had a paraconduit hernia (15%) compared with 16 of 212 open or hybrid esophagectomies (8%; P = .03). Hernias were symptomatic in 13 patients (36%) and asymptomatic in 23 (64%), which were detected radiographically. Repair was performed in 11 of 13 symptomatic patients (85%), compared with 3 of 23 asymptomatic patients (13%). In the asymptomatic group, only 1 required emergency repair (4.3%). There was a trend toward a greater proportion of symptomatic paraconduit hernias compared with asymptomatic patients (77% versus 43%; P = .08) in MIE patients. Factors associated with the development of paraconduit hernias on univariate analysis were younger age (P = .02) and not receiving neoadjuvant chemotherapy (P = .01) or neoadjuvant radiation (P = .03).

Conclusions: Postesophagectomy paraconduit hernia is more common after totally minimally invasive esophagectomy compared with open or hybrid techniques. One third are symptomatic and the remainder are detected only radiographically. Repair of asymptomatic hernias consider the patient's cancer prognosis.
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http://dx.doi.org/10.1016/j.athoracsur.2020.07.047DOI Listing
June 2021

Early Rescue from Acute Severe Clostridium Difficile: A Novel Treatment Strategy.

Surg Infect (Larchmt) 2018 Jan 11;19(1):78-82. Epub 2017 Dec 11.

1 Division of General Surgery, Western University , London, Ontario, Canada .

Background: Severe Clostridium difficile infections (CDI) can lead to significant impediments to effective treatment. We developed a novel treatment protocol utilizing bedside gastrointestinal lavage (GIL) for the management of patients with severe, complicated CDI. We describe the development and early outcomes of non-operative bedside GIL in hospitalized patients with severe, complicated CDI following the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework at the Idea stage. We compared our results with those of a cohort of patients managed with colectomy.

Methods: We conducted a retrospective cohort study of hospitalized patients with severe, complicated CDI who failed conventional medical therapy and were referred for surgical consultation at two academic tertiary-care hospitals between January 2009 and January 2015. After surgical assessment, the attending surgeon decided to proceed either with bedside GIL or directly to colectomy. Bedside GIL involved nasojejunal tube insertion followed by flushing with 8 L of polyethylene glycol 3350/electrolyte solution over 48 h. Both patient groups received standard medical treatment with vancomycin 500 mg q 6 h enterally and metronidazole 500 mg intravenously three times daily for 14 d. The main outcomes of interest were the incidence of colectomy, complications, and mortality rate.

Results: Nineteen and seventeen patients underwent GIL and direct colectomy, respectively. There were no significant differences between the groups in terms of demographics, American Society of Anesthesiologists class, disease severity, need for intensive care unit admission, mechanical ventilation, vasopressor use, serum lactate concentration, or proportion presenting with hypotension, acute kidney injury, or a white blood cell count >16,000/mcL or <4,000/mcL (p > 0.1). The in-hospital mortality rate was 26% (5/19) and 41% (7/17) for the GIL and colectomy groups, respectively (p = 0.35). Only one patient in the GIL group failed the protocol, requiring colectomy. There were no significant differences in complications in the two groups.

Conclusions: Bedside GIL appeared to be safe for the treatment of patients with severe, complicated CDI who had failed conventional medical therapy. It did not appear to increase the risk of morbidity or death compared with the traditional strategy of proceeding directly to colectomy.
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http://dx.doi.org/10.1089/sur.2017.147DOI Listing
January 2018

ALPPS: challenging the concept of unresectability--a systematic review.

Int J Surg 2015 Jan 11;13:280-287. Epub 2014 Dec 11.

Department of Surgery, Schulich School of Medicine & Dentistry, University of Western Ontario, 339 Windermere Road, London, ON, Canada N6A 5A5; Multi-Organ Transplant Program, London Health Sciences Centre, 339 Windermere Road, London, ON, Canada N6A 5A5. Electronic address:

Introduction: Hepatic resection for malignancy is limited by the amount of liver parenchyma left behind. As a result, two-staged hepatectomy and portal vein occlusion (PVO) have become part of the treatment algorithm. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been recently described as a method to stimulate rapid and profound hypertrophy.

Materials And Methods: A systematic review of the literature pertaining to ALPPS was undertaken. Peer-reviewed articles relating to portal vein ligation (PVL) and in situ split (ISS) of the parenchyma were included.

Results: To date, ALPPS has been employed for a variety of primary and metastatic liver tumors. In early case series, the perioperative morbidity and mortality was unacceptably high. However with careful patient selection and improved technique, many centers have reported a 0% 90-day mortality. The benefits of ALPPS include hypertrophy of 61-93% over a median 9-14 days, 95-100% completion of the second stage, and high likelihood of R0 resection (86-100%).

Discussion: ALPPS is only indicated when a two-stage hepatectomy is necessary and the future liver remnant (FLR) is deemed inadequate (<30%). Use in patients with poor functional status, or advanced age (>70 years) is cautioned. Discretion should be used when considering this in patients with pathology other than colorectal liver metastases (CRLM), especially hilar tumors requiring biliary reconstruction. Biliary ligation during the first stage and routine lymphadenectomy of the hepatoduodenal ligament should be avoided.

Conclusions: A consensus on the indications and contraindications for ALPPS and a standardized operative protocol are needed.
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http://dx.doi.org/10.1016/j.ijsu.2014.12.008DOI Listing
January 2015

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

PLoS One 2013 9;8(9):e72668. Epub 2013 Sep 9.

Department of Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV) block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.

Methodology/principal Findings: We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene) in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis and immunofluorescence (IF) staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I). Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved) of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN) cells.

Conclusions/significance: Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072668PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767782PMC
June 2014

Bone marrow-derived progenitor cells in end-stage lung disease patients.

BMC Pulm Med 2013 Aug 3;13:48. Epub 2013 Aug 3.

Latner Thoracic Surgery Research Laboratories, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, North Wing, 9N - 949, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada.

Background: Chronic lung diseases are marked by progressive inflammation, tissue damage and remodelling. Bone marrow-derived progenitor cells may contribute to these processes. The objectives of this study were to (1) to quantify CD45⁺Collagen-1⁺ fibrocytes and a novel epithelial-like population of bone marrow-derived cells, which express Clara Cell Secretory Protein, in patients at the time of lung transplant and (2) to evaluate mediators that may act to recruit these cells during injury.

Methods: Using an observational design, progenitor cells were quantified by flow cytometry from both bone marrow (BM) and peripheral blood (PB). Migration was tested using in vitro transwell assays. Multiplex bead-based assays were used to quantify plasma cytokines.

Results: An increase in CD45⁺Collagen-1⁺ fibrocytes was found in pulmonary fibrosis and bronchiolitis obliterans patients. Cystic fibrosis patients had an increase in CCSP⁺ cells in both the BM and PB. The proportion of CCSP⁺ cells in the BM and PB was correlated. CCSP+ cells express the chemokine receptors CCR2, CCR4, CXCR3, and CXCR4, and significantly migrated in vitro toward Stromal Derived Factor-1 (SDF-1) and Stem Cell Growth Factor-β (SCGF-β). Plasma cytokine levels differed between disease groups, with a significant correlation between SCGF-β and CCSP⁺ cells and between Monocyte Chemotactic Protein-1 and fibrocytes.

Conclusions: Different bone marrow-derived cells are found in various lung diseases. Increased fibrocytes were associated with fibrotic lung diseases. An increase in the novel CCSP⁺ epithelial-like progenitors in cystic fibrosis patients was found. These differences may be mediated by alterations in plasma cytokines responsible for cell recruitment.
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http://dx.doi.org/10.1186/1471-2466-13-48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750607PMC
August 2013

Altered progenitor cell and cytokine profiles in bronchiolitis obliterans syndrome.

J Heart Lung Transplant 2012 Feb;31(2):222-8

University Health Network, Latner Thoracic Surgery Research Laboratories, University of Toronto, Toronto, Ontario, Canada.

Background: Bone marrow-derived progenitor cells may play a key role in both lung repair and in fibrogenesis. The contribution of CD45(+)collagen-1(+) fibrocytes to fibrosis has been documented elsewhere and recently identified epithelial-like progenitor cells marked by Clara cell secretory protein (CCSP(+)) may be protective after lung injury. Interplay between these populations has not yet been studied in bronchiolitis obliterans syndrome (BOS) post-lung transplant.

Methods: In a cross-sectional design, blood samples were analyzed for CCSP(+) cells and CD45(+)collagen-1(+) fibrocytes by flow cytometry. Plasma cytokines were analyzed by multiplex array.

Results: A higher proportion of circulating fibrocytes was measured in patients with BOS Grade ≥1 than in those with BOS Grade 0(p). In parallel, a lower proportion of CCSP(+) cells was found in BOS ≥1 patients compared with BOS 0(p) and non-transplant controls, resulting in an altered cell ratio between the groups. A higher ratio of CD45(+)collagen-1(+) to CCSP(+) cells was associated with greater airflow limitation based on FEV(1) and FEV(1)/FVC ratio. No relationship between cell profiles and time post-transplant was found. Plasma analysis showed an increase in key stem cell and inflammatory cytokines in both groups post-transplant, whereas stromal-derived factor-1 and vascular endothelial growth factor were increased in cases of BOS ≥1 specifically. Plasma stromal-derived factor-1 levels also correlated with fibrocytes post-transplant.

Conclusions: Overall, altered progenitor cell profiles were found in patients who developed advanced BOS, which may be mediated by alterations in circulating cytokines. Ultimately, measurement of progenitor cell profiles may lead to further insight into the pathogenesis of airflow obstruction after lung transplantation.
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http://dx.doi.org/10.1016/j.healun.2011.11.012DOI Listing
February 2012
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