Donor leukocyte trafficking during human ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) is used to assess and preserve lungs prior to transplantation. However, its inherent immunomodulatory effects are not completely understood. We examine perfusate and tissue compartments to determine the change in immune cell composition in human lungs maintained on EVLP. METHODS: Six human lungs unsuitable for transplantation underwent EVLP. Tissue and perfusate samples were obtained during cold storage and at 1-, 3- and 6-h during perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines. Mean values between baseline and time points were compared by Student's t test. RESULTS: During the 1st hour of perfusion, perfusate neutrophils increased (+22.2 ± 13.5%, p < 0.05), monocytes decreased (-77.5 ± 8.6%, p < 0.01) and NK cells decreased (-61.5 ± 22.6%, p < 0.01) compared to cold storage. In contrast, tissue neutrophils decreased (-22.1 ± 12.2%, p < 0.05) with no change in monocytes and NK cells. By 6 h, perfusate neutrophils, NK cells, and tissue neutrophils were similar to baseline. Perfusate monocytes remained decreased, while tissue monocytes remained unchanged. There was no significant change in B cells or T cell subsets. Pro-inflammatory cytokines (IL-1b, G-CSF, IFN-gamma, CXCL2, CXCL1 granzyme A, and granzyme B) and lymphocyte activating cytokines (IL-2, IL-4, IL-6, IL-8) increased during perfusion. CONCLUSIONS: Early mobilization of innate immune cells occurs in both perfusate and tissue compartments during EVLP, with neutrophils and NK cells returning to baseline and monocytes remaining depleted after 6 h. The immunomodulatory effect of EVLP may provide a therapeutic window to decrease the immunogenicity of lungs prior to transplantation.

The risk analysis index is an independent predictor of outcomes after lung cancer resection.

BACKGROUND: The Risk Analysis Index (RAI) is a frailty assessment tool based on an accumulation of deficits model. We mapped RAI to data from the Society of Thoracic Surgeons (STS) Database to determine whether RAI correlates with postoperative outcomes following lung cancer resection. METHODOLOGY/PRINCIPAL FINDINGS: This was a national database retrospective observational study based on data from the STS Database. Study patients underwent surgery 2018 to 2020. RAI was divided into four increasing risk categories. The associations between RAI and each of postoperative complications and administrative outcomes were examined using logistic regression models. We also compared the performance of RAI to established risk indices (American Society of Anesthesiology (ASA) and Charlson Comorbidity Index (CCI)) using areas under the Receiver Operating Characteristic (ROC) curves (AUC). Results: Of 29,420 candidate patients identified in the STS Database, RAI could be calculated for 22,848 (78%). Almost all outcome categories exhibited a progressive increase in marginal probability as RAI increased. On multivariable analyses, RAI was significantly associated with an incremental pattern with almost all outcomes. ROC analyses for RAI demonstrated "good" AUC values for mortality (0.785; 0.748) and discharge location (0.791), but only "fair" values for all other outcome categories (0.618 to 0.690). RAI performed similarly to ASA and CCI in terms of AUC score categories. CONCLUSIONS/SIGNIFICANCE: RAI is associated with clinical and administrative outcomes following lung cancer resection. However, its overall accuracy as a surgical risk predictor is only moderate and similar to ASA and CCI. We do not recommend routine use of RAI for assessment of individual patient risk for major lung resection.

Gender Bias in Judging Frailty and Fitness for Lung Surgery.

BACKGROUND: Disparities in surgical care for lung cancer have been well documented, and unconscious bias may be a source of inequity. We assessed whether gender biases exist when nonclinical decision makers render decisions about major lung surgery. METHODS: Amazon Mechanical Turk workers, remotely located "crowdworkers" readily available for hire to perform discrete on-demand tasks on the Amazon Mechanical Turk platform, were each shown 4 videos of different standardized patients (SPs) in a clinic setting, 1 video in each energy level (vigorous or frail) and race category (White or Black), randomized to male or female. Workers scored video characteristics and whether they would support the SP's decision to undergo a major lung operation. RESULTS: A total of 855 workers were recruited. The frail White male SP was more likely to have support to undergo lung surgery than the frail White female SP, while the frail Black male SP was much less likely to have support to undergo lung surgery than the frail Black female SP. There were no significant differences in support for surgery between the vigorous male and female SPs and ratings by male and female workers in their recommendations. CONCLUSIONS: Biases related to patient gender exist in the general population and affect views on surgery, particularly in the setting of frailty. Understanding such differences may aid in educational efforts directed at reducing gender-based biases in treatment recommendations.

Thoracoscopic sympathectomy decreases disease burden in patients with medically refractory ventricular arrhythmias.

OBJECTIVES: Thoracic sympathectomy has been shown to be effective in reducing implantable cardioverter-defibrillator (ICD) shocks and ventricular tachycardia recurrence in patients with channelopathies, but the evidence supporting its use for refractory ventricular arrhythmias in patients without channelopathies is limited. This is a single-centre cohort study of bilateral R1-R4 thoracoscopic sympathectomy for medically refractory ventricular arrhythmias. METHODS: Clinical information was examined for all bilateral thoracoscopic R1-R4 sympathectomies for ventricular arrhythmias at our institution from 2016 through 2020. RESULTS: Thirteen patients underwent bilateral thoracoscopic R1-R4 sympathectomy. All patients had prior ICD implant. Patients had a recent history of multiple ICD discharges (12/13), catheter ablation (10/13) and cardiac arrest (3/13). Ten patients were urgently operated on following transfer to our centre for sustained ventricular tachycardia. Seven patients had ventricular tachycardia ablations preoperatively during the same admission. Five patients were in intensive care immediately preoperatively, with 3 requiring mechanical ventilation. Three patients suffered in-hospital mortality. Kaplan-Meier analysis estimated 73% overall survival at 24-month follow-up. Among the 10 patients who survived to discharge, all were alive at a median follow-up of 8.7 months (interquartile range 0.6-26.7 months). Six of 10 patients had no further ICD discharges. Kaplan-Meier analysis estimated 27% ICD shock-free survival at 24 months follow-up for all patients. Three of 10 patients had additional ablations, while 2 patients underwent cardiac transplantation. CONCLUSIONS: Bilateral thoracoscopic sympathectomy is an effective option for patients with life-threatening ventricular arrhythmia refractory to pharmacotherapy and catheter ablation.

Knowledge of surgical management of hyperhidrosis among primary care physicians and the general public.

OBJECTIVES: Our study examined attitudes towards initial management of hyperhidrosis, willingness to seek surgical consultation and knowledge of an appropriate specialty for surgical consultation among primary care physicians and the general public. METHODS: An online survey was sent to all general medicine and paediatric residents and attending physicians at our academic medical centre. Participants were provided with a clinical scenario of palmar hyperhidrosis and were asked to select among initial management options and preferences for surgical consultation if patients failed non-operative management. To assess the general public's perspective, workers from Amazon Mechanical Turk were recruited to complete a similar survey. RESULTS: The majority of primary care physicians (31/53; 58%) would prescribe topical aluminium chloride for palmar hyperhidrosis, whereas 28 of 53 (53%) would refer such patients to dermatology. Twenty-three of 53 (43%) physicians would refer such patients to surgery if conservative management failed: 18 (78%) to plastic surgery, 4 (17%) to general surgery and none to thoracic surgery. The majority of workers (130/205; 63.4%) would seek primary care treatment for palmar hyperhidrosis. Over half (113/205; 55%) would seek surgical consultation if conservative management failed: 65 (58%) general surgery and 15 (13%) neurosurgery, with only 8 (7%) selecting thoracic surgery. CONCLUSIONS: Neither primary care physicians nor the general public recognize the role of thoracic surgeons in managing primary focal hyperhidrosis when medical management fails. Education of physicians and the public may mitigate this knowledge gap.

Frailty Is Associated With Adverse Postoperative Outcomes After Lung Cancer Resection.

Introduction: Frailty is an important predictor of outcomes after noncardiac surgery. The 5-factor Modified Frailty Index (mFI-5) is a recently developed frailty metric that has not been adequately evaluated in relation to surgical therapy for lung cancer. We evaluated whether the mFI-5 is predictive of clinical and administrative outcomes after anatomical lung resection for cancer. Methods: Data in the Society of Thoracic Surgeons Database were used to evaluate the relationship of mFI-5 to outcomes of patients undergoing elective anatomical lung resection for cancer from 2015 to 2018 using logistic regression analyses. Results were compared with validated risk predictors, including the American Society of Anesthesiologists Physical Status Classification and the Charlson Comorbidity Index. Results: The mFI-5 score could be calculated for 36,587 patients. On univariate analyses, mFI-5 was significantly associated with all clinical and administrative outcomes in an incremental pattern (p < 0.0001 for each). On multivariate analyses, mFI-5 was significantly associated in an incremental pattern with 13 of 15 postoperative complication and administrative outcome categories; the exceptions were cardiovascular complications and 30-day mortality. The overall performance of the frailty metric mFI-5 was similar to that of the American Society of Anesthesiologists and the Charlson Comorbidity Index. Conclusions: The mFI-5 is independently predictive of almost all outcomes after lung resection for cancer. It can be calculated from data typically collected for thoracic surgical patients. Assessment of surgical candidates using mFI-5 may be useful in risk prediction and may identify patients who would benefit from mitigation of increased surgical risk related to frailty.

Lung resection surgery in Jehovah's Witness patients: a 20-year single-center experience.

BACKGROUND: The paucity of literature on surgical outcomes of Jehovah's Witness (JW) patients undergoing lung resection suggests some patients with operable lung cancers may be denied resection. The aim of this study is to better understand perioperative outcomes and long-term cancer survival of JW patients undergoing lung resection. METHODS: All pulmonary resections in JW patients at one institution from 2000 through 2020 were examined. Demographics, comorbidities, operative parameters, and perioperative outcomes were reviewed. Among operations performed for primary non-small cell lung cancer (NSCLC), details regarding staging, extent of resection, additional therapies, recurrence, and survival were abstracted. RESULTS: Seventeen lung resections were performed in fourteen patients. There were nine anatomic resections and eight wedge resections. Fourteen resections (82%) were approached thoracoscopically, of which 3 of 6 anatomic resections were converted to thoracotomy as compared to 1 of 8 wedge resections. There was one (6%) perioperative death. Ten resections in 8 patients were performed for primary pulmonary malignancies, and two patients underwent procedures for recurrent disease. Median survival for resected NSCLCs (N = 7) was 65 months. Three of 6 patients who survived the immediate perioperative period underwent additional procedures: 2 pulmonary wedge resections for diagnosis and one pleural biopsy. CONCLUSIONS: This series of JW patients undergoing lung resections demonstrates that resections for cancer and inflammatory etiologies can be performed safely in the setting of both primary and re-operative procedures.

Recent Changes in Characteristics of Applicants and Matriculants to Thoracic Surgery Fellowships.

The match rate for traditional thoracic surgery fellowships decreased from 97.5% in 2012 to 59.1% in 2021, reflecting an increase in applications. We queried whether characteristics of applicants and matriculants to traditional thoracic surgery fellowships changed during this time period. Applicant data from the 2008 through 2018 application cycles were extracted from the Electronic Residency Application System (ERAS) and Graduate Medical Education (GME) Track Resident Survey and stratified by period of application (2008-2014 vs 2015-2018). Characteristics of applicants and matriculants were analyzed. There were 697 applicant records in the early period and 530 in the recent period (application rate 99.6/year vs 132.5/year; P = 0.0005), and 607 matriculant records in the early period and 383 in the recent period (matriculation rate 87% vs 72%; P < 0.0001). There was no difference in representation of university-affiliated versus community-based general surgery residency programs among applicants comparing the periods. Higher proportions of applicants and matriculants in the early period trained in general surgery programs affiliated with a comprehensive cancer center or a thoracic surgery fellowship. Applicants and matriculants of the recent period had higher median numbers of journal publications and had higher impact factor journal publications. The increase in applicants for thoracic surgery training is primarily from general surgery trainees in residency programs not affiliated with a comprehensive cancer center or a thoracic surgery fellowship. The increased interest in thoracic surgery training was accompanied by overall enhanced scholarship production among the applicants and matriculants regardless of their residency characteristics.

Surgical Transcatheter Aortic Valve Replacement Explantation Technique.

As transcatheter aortic valve replacement (TAVR) indications expand, cardiac surgeons need to be prepared to manage heretofore rare TAVR complications requiring explantation, such as acute type A dissection, in these typically high-risk patients. This report describes the successful use of an explantation technique that is ready to hand, efficient, and effective at avoiding further injury to the aortic root and coronary ostia.

The Effect of Normothermic Machine Perfusion on the Immune Profile of Donor Liver.

Background: Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP. Methods: Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student's t-test. Results: Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion. Conclusions: Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.

Infected port-a-cath leading to subpectoral and sterno-manubrial abscess.

Sterno-manubrium and subpectoral abscess have been rarely reported in literature. If the diagnosis and treatment are not properly performed, a soft tissue abscess can cause serious complications such as sepsis or even death. Therefore, awareness of such conditions is essential for early diagnosis and prompt treatment. Here, we report a case of sterno-manubrial and subpectoral abscess with significant destruction of cartilage due to extension from an infected subclavian porta-a-cath. Our management started with intravenous antibiotic therapy initially; however, due to lack of clinical resolution, incision and drainage followed by serial debridements were performed, highlighting importance of awareness of uncommon presentation.

Surgical management of locally invasive basaloid carcinoma of thymic gland.

Thymic basaloid carcinoma is an extremely rare thymic tumor variant, and the most common presentations have been an incidental finding on a routine chest X-ray and dyspnea on exertion. Given its rarity, no treatment modalities have been demonstrated to improve survival. This rare case describes a patient with locally advanced thymic basaloid carcinoma treated by en bloc resection of phrenic nerve and left upper lobe with the tumor followed by adjuvant radiation therapy. Patient had no respiratory complaints at 10 months follow-up, and 10-month post-operative surveillance radiological study showed no objective sign of tumor recurrence.

Nanotraps for the containment and clearance of SARS-CoV-2.

SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed "Nanotraps," completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudotyped and authentic virus in vitro. Furthermore, the Nanotraps demonstrated an excellent biosafety profile in vitro and in vivo. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an ex vivo lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.