Predictors of Cytomegalovirus Recurrence Following Cessation of Posttransplant Prophylaxis.

INTRODUCTION: Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation. CMV prophylaxis is commonly administered in the first year following transplantation to reduce CMV infection; however, the risk factors for long-term reactivation remain unclear. We investigated the timing and risk factors of CMV infection after prophylactic administration. METHODS: This study was a retrospective review of the institutional lung transplantation database from June 2014 to June 2022. Data on patient characteristics, pretransplantation laboratory values, postoperative outcomes, and CMV infection were collected. Donor CMV-IgG-positive and recipient CMV-IgG-negative groups were defined as the CMV mismatch group. RESULTS: During the study period, 257 patients underwent lung transplantation and received a prophylactic dose of valganciclovir hydrochloride for up to 1 y. CMV infection was detected in 69 patients (26.8%): 40 of 203 (19.7%) in the non-CMV mismatch group and 29 of 54 (53.7%) in the CMV mismatch group (P < 0.001). CMV infection after prophylaxis occurred at a median of 425 and 455 d in the CMV mismatch and non-CMV mismatch groups, respectively (P = 0.07). Multivariate logistic regression analysis revealed that preoperative albumin level (odds ratio [OR] = 0.39, P = 0.04), CMV mismatch (OR = 15.7, P < 0.001), and donor age (OR = 1.05, P = 0.009) were significantly associated with CMV infection. CONCLUSIONS: CMV mismatch may have increased the risk of CMV infection after lung transplantation, which decreased after prophylaxis. In addition to CMV mismatch, low preoperative albumin level and donor age were independent predictors of CMV infection.

Residents Need a Dynamic Approach to Leadership Education: A Qualitative Study.

OBJECTIVE: Leadership is an essential skill for surgeons, but it is not systematically taught in residency. The objective of this study was to explore the current experiences, motivators, and perspectives on leadership training of general surgery residents. DESIGN/SETTING/PARTICIPANTS: Semi-structured focus groups were conducted with 20 general surgery residents at an academic training program. Six in-person sessions (one for each postgraduate year and research) were recorded, transcribed, and de-identified. Data were inductively coded by 2 independent researchers and analyzed thematically. Discrepancies were discussed and resolved through consensus. RESULTS: Participants described developing their leadership skills prior to residency through formal (e.g., job and military) and informal (e.g., extracurricular) experiences. Most reported that leadership development during residency occurred informally (e.g., emulating mentors, trial-and-error). Evolving responsibilities and expectations shaped residents' leadership values: junior residents focused on student and task management and adaptation to new teams; mid-level residents emphasized emotional intelligence and delivery of resident feedback; and senior residents stressed team engagement, inspiring the team, and teaching/mentoring. Major transition periods between residency levels were identified as critical times for leadership training as they allow for self-reflection, motivating residents to participate in a leadership curriculum. Employing level appropriate and immediately applicable content during this time would encourage curriculum attendance and prepare residents for new roles. CONCLUSIONS: There is a lack of formal leadership training in general surgery residency. There is an opportunity to design and implement leadership training that engages surgical residents with level-relevant content and strategies. Transition periods offer optimal timing for maximal curricula uptake.

Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts.

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

The impact of procedural activities on musculoskeletal pain experienced by pregnant surgeons.

BACKGROUND: Two-thirds of surgeons report work-related musculoskeletal disorders (WRMD). There is limited data on WRMD symptoms experienced by pregnant surgeons. METHODS: We distributed an electronic survey via personal contacts to attending and trainee surgeons across six academic institutions to assess the impact of procedural activities and surgical ergonomics (SE) on WRMD symptoms during pregnancy. RESULTS: Fifty-three respondents were currently or had been pregnant while clinically active, representing 93 total pregnancies. 94.7% reported that symptoms were exacerbated by workplace activities during pregnancy and 13.2% took unplanned time off work as a result. Beyond 24 weeks of pregnancy, 89.2% of respondents continued to operate/perform procedures, 81.7% worked >24-h shifts and 69.9% performed repetitive lifting >50 pounds. No respondents were aware of any institutional pregnancy-specific SE policies. CONCLUSIONS: Procedural activities can exacerbate pain symptoms for the pregnant surgeon. SE best practices during pregnancy warrant further attention.

Wireless broadband acousto-mechanical sensing system for continuous physiological monitoring.

The human body generates various forms of subtle, broadband acousto-mechanical signals that contain information on cardiorespiratory and gastrointestinal health with potential application for continuous physiological monitoring. Existing device options, ranging from digital stethoscopes to inertial measurement units, offer useful capabilities but have disadvantages such as restricted measurement locations that prevent continuous, longitudinal tracking and that constrain their use to controlled environments. Here we present a wireless, broadband acousto-mechanical sensing network that circumvents these limitations and provides information on processes including slow movements within the body, digestive activity, respiratory sounds and cardiac cycles, all with clinical grade accuracy and independent of artifacts from ambient sounds. This system can also perform spatiotemporal mapping of the dynamics of gastrointestinal processes and airflow into and out of the lungs. To demonstrate the capabilities of this system we used it to monitor constrained respiratory airflow and intestinal motility in neonates in the neonatal intensive care unit (n = 15), and to assess regional lung function in patients undergoing thoracic surgery (n = 55). This broadband acousto-mechanical sensing system holds the potential to help mitigate cardiorespiratory instability and manage disease progression in patients through continuous monitoring of physiological signals, in both the clinical and nonclinical setting.

Single-Center Experience With Lung Transplant Evaluation Referrals of Acute Respiratory Distress Syndrome Patients During the COVID-19 Pandemic: How Do You Make Up For Lost Time?

Transfer of select, medically refractory acute respiratory distress syndrome patients to lung transplant centers requires extensive resources. Here, we report 270 consecutive lung transplant patient referrals to our center for medically refractory ARDS from June 2021 to April 2022, following the implementation of clinical care pathways for intake of these patients. Eighty-seven of 270 patients (32.2%) met screening criteria and were evaluated for transfer within a median of 12 days, during which 38 of 87 patients (43.7%) died and 12 of 87 patients (13.8%) transferred elsewhere. Thirty-seven of 87 patients (42.5%) were accepted for transfer of which 16 of 37 patients (43.2%) successfully transferred to our center with a median transfer waiting period of 12 days. Because of resource constraints, 21 of 37 accepted patients (56.8%) could not be transferred of which 9 of 21 patients (42.9%) died while waiting. Nine of 16 transferred patients (56.2%) eventually underwent lung transplantation with over 80% 6-month survival. ARDS patients referred for transplantation have high risk of mortality and, therefore, require well-described pathways for evaluation and transfer.

Primary graft dysfunction grade correlates with acute kidney injury stage after lung transplantation.

Background: Primary graft dysfunction (PGD) and acute kidney injury (AKI) are major early complications of lung transplantation and are associated with increased mortality. Lung injury after PGD can contribute to renal dysfunction; however, the association between PGD and AKI severity has not been thoroughly investigated. We analyzed the association between PGD grading and AKI staging, and the impact of AKI on subsequent changes to chronic kidney disease (CKD), including glomerular filtration rate (GFR), over time. Methods: This was a retrospective review of a single-center lung transplantation database between January 2018 and June 2022. AKI and GFR categories were classified according to the Kidney Disease: Improving Global Outcomes criteria. Spearman's and Kaplan-Meier tests were used to compare disease severity and assess survival. Results: In a total of 206 patients: 119 (57.8%), 25 (12.1%), 34 (16.5%), and 28 (13.6%) had PGD grades 0, 1, 2, and 3, respectively; 96 (46.6%), 47 (22.8%), 27 (13.1%), and 36 (17.5%) had AKI stages 0, 1, 2, and 3, respectively. Twenty-one of the 28 patients (75.0%) with PGD grade 3 had AKI stage 3. There was a significant correlation between PGD grade and AKI stage (P<0.001). There was also a significant correlation between AKI stage and GFR category of CKD at 3, 6, 9, and 12 months after lung transplantation (all P<0.001). For all AKI stages, GFR categories worsened with postoperative time. Conclusions: PGD grade was significantly correlated with AKI stage, and AKI stage was correlated with GFR categories of CKD.

Lung transplantation for coronavirus disease 2019 acute respiratory distress syndrome/fibrosis: silver lining of a global pandemic.

PURPOSE OF REVIEW: The COVID-19 pandemic revolutionized the field of lung transplantation, as lung transplant is now an acceptable life-saving therapy for select patients with COVID-19-associated acute respiratory distress syndrome (ARDS), while prior to the pandemic, few transplants were performed for ARDS. This review article details the establishment of lung transplantation as a viable therapy for COVID-19-related respiratory failure, how to evaluate COVID-19 patients for lung transplant, and specific technical considerations for the operation. RECENT FINDINGS: Lung transplantation is a life-altering treatment for two distinct cohorts of COVID-19 patients: those with irrecoverable COVID-19-associated ARDS and those who recover from the initial COVID-19 insult but are left with chronic, debilitating post-COVID fibrosis. Both cohorts require stringent selection criteria and extensive evaluation to be listed for lung transplantation. As the first COVID-19 lung transplantation was recently performed, long-term outcomes are lacking; however, short-term outcome data of COVID-19-related lung transplants are promising. SUMMARY: Given the challenges and complexities associated with COVID-19-related lung transplantation, strict patient selection and evaluation are required with an experienced multidisciplinary team at a high-volume/resource center. With promising short-term outcome data, ongoing studies are needed to assess long-term outcomes of COVID-19-related lung transplants.

Lung Transplantation in Coronavirus-19 Patients: What We Have Learned So Far.

Coronavirus-19 (COVID-19) can result in irrecoverable acute respiratory distress syndrome (ARDS) or life-limiting fibrosis for which lung transplantation is currently the only viable treatment. COVID-19 lung transplantation has transformed the field of lung transplantation, as before the pandemic, few transplants had been performed in the setting of infectious disease or ARDS. Given the complexities associated with COVID-19 lung transplantation, it requires strict patient selection with an experienced multidisciplinary team in a high-resource hospital setting. Current short-term outcomes of COVID-19 lung transplantation are promising. However, follow-up studies are needed to determine long-term outcomes and whether these patients may be predisposed to unique complications.

Recipient, donor, and surgical factors leading to primary graft dysfunction after lung transplant.

Background: Primary graft dysfunction is a major cause of early mortality following lung transplantation. The International Society for Heart and Lung Transplantation subdivides it into 4 grades of increasing severity. Methods: A retrospective review of the institutional lung transplant database from March 2018 to September 2021 was performed. Patients were stratified into three groups: primary graft dysfunction grade 0 patients, grade 1 or 2 patients, and grade 3 patients. Recipient, donor, and surgical variables were analyzed by logistic regression analysis to identify risk factors for primary graft dysfunction grade 1 or 2 and grade 3. Results: Primary graft dysfunction grade 1 to 3 occurred in 45.0% of the cohort (n=68) of whom 33.3% (n=23) had primary graft dysfunction grade 3. Longer operative time was more common in primary graft dysfunction grade 1 to 3 patients (P<0.001). The 1-year survival of the patients with primary graft dysfunction grade 3 was lower than the others (grade 0-2 vs. 3, 93.7% vs. 65.2%, P=0.0006). Univariate analysis showed that acute respiratory distress syndrome, operative time, and intraoperative veno-arterial extracorporeal membrane oxygenation use were risk factors for primary graft dysfunction grades 1 or 2 and grade 3. Multivariate analysis identified that intraoperative veno-arterial extracorporeal membrane oxygenation use was an independent risk factor of primary graft dysfunction grade 1 or 2. Patients with an operative time of more than 8.18 hours had significantly higher incidence of primary graft dysfunction grade 3, acute kidney injury, and digital ischemia. Conclusions: The calculated predictors of primary graft dysfunction grade 1 or 2 were similar to those of primary graft dysfunction grade 3.

Early initiation of physical and occupational therapy while on extracorporeal life support improves patients' functional activity.

PURPOSE: Managing acute respiratory distress syndrome (ARDS) patients on venovenous extracorporeal membrane oxygenation (V-V ECMO), without sedation/neuromuscular blockade to allow physical and occupational therapy (PT/OT) participation, is untraditional. Here, we investigate the impact of early PT/OT initiation on discharge functional activity for ARDS patients managed on V-V ECMO. METHODS: This is a retrospective review of 67 ARDS patients managed with V-V ECMO at a single academic center from February 2018 to June 2021. Data collected included patient characteristics, days of V-V ECMO support, day of PT/OT initiation, and ambulation distance and Activity Measure for Post-Acute Care (AMPAC) Six-Clicks score on day of discharge. RESULTS: Patients with >7 days of V-V ECMO support had decreased ambulation and AMPAC scores compared to those with <7 days (70.5 vs. 162.1, p < 0.01 and 12.3 vs. 16.4, p = 0.01, respectively). PT/OT initiation within 7 days after starting V-V ECMO significantly improved ambulation and AMPAC scores (163.5 vs. 59.5, p < 0.001, and 16.6 vs. 11.8, p < 0.01, respectively). Additionally, in patients with >7 days of V-V ECMO support, those who began PT/OT within 8 days of V-V ECMO cannulation had significantly improved ambulation and AMPAC scores (151.8 vs. 44.2, p < 0.01, and 16.5 vs. 11.0, p < 0.01, respectively). CONCLUSION: Early PT/OT initiation in severe ARDS patients managed on V-V ECMO is associated with improved patient functional activity on day of discharge. Our study further supports the use of V-V ECMO in treatment of severe ARDS without sedation/neuromuscular blockade and specifically demonstrates PT/OT should be started early following V-V ECMO cannulation.

Postreperfusion Pulmonary Artery Pressure Indicates Primary Graft Dysfunction After Lung Transplant.

BACKGROUND: Primary graft dysfunction is a risk factor of early mortality after lung transplant. Models identifying patients at high risk for primary graft dysfunction are limited. We hypothesize high postreperfusion systolic pulmonary artery pressure is a clinical marker for primary graft dysfunction. METHODS: This is a retrospective review of 158 consecutive lung transplants performed at a single academic center from January 2020 through July 2022. Only bilateral lung transplants were included and patients with pretransplant extracorporeal life support were excluded. RESULTS: Primary graft dysfunction occurred in 42.3% (n = 30). Patients with primary graft dysfunction had higher postreperfusion systolic pulmonary artery pressure (41 ± 9.1 mm Hg) than those without (31.5 ± 8.8 mm Hg) (P < .001). Logistic regression showed postreperfusion systolic pulmonary artery pressure is a predictor for primary graft dysfunction (odds ratio 1.14, 95% CI 1.06-1.24, P < .001). Postreperfusion systolic pulmonary artery pressure of 37 mm Hg was optimal for predicting primary graft dysfunction by Youden index. The receiver operating characteristic curve of postreperfusion systolic pulmonary artery pressure at 37 mm Hg (sensitivity 0.77, specificity 0.78, area under the curve 0.81), was superior to the prereperfusion pressure curve at 36 mm Hg (sensitivity 0.77, specificity 0.39, area under the curve 0.57) (P < .01). CONCLUSIONS: Elevated postreperfusion systolic pulmonary artery pressure after lung transplant is predictive of primary graft dysfunction. Postreperfusion systolic pulmonary artery pressure is more indicative of primary graft dysfunction than prereperfusion systolic pulmonary artery pressure. Using postreperfusion systolic pulmonary artery pressure as a positive signal of primary graft dysfunction allows earlier intervention, which could improve outcomes.

IL-1ß-dependent extravasation of preexisting lung-restricted autoantibodies during lung transplantation activates complement and mediates primary graft dysfunction.

Preexisting lung-restricted autoantibodies (LRAs) are associated with a higher incidence of primary graft dysfunction (PGD), although it remains unclear whether LRAs can drive its pathogenesis. In syngeneic murine left lung transplant recipients, preexisting LRAs worsened graft dysfunction, which was evident by impaired gas exchange, increased pulmonary edema, and activation of damage-associated pathways in lung epithelial cells. LRA-mediated injury was distinct from ischemia-reperfusion injury since deletion of donor nonclassical monocytes and host neutrophils could not prevent graft dysfunction in LRA-pretreated recipients. Whole LRA IgG molecules were necessary for lung injury, which was mediated by the classical and alternative complement pathways and reversed by complement inhibition. However, deletion of Fc receptors in donor macrophages or mannose-binding lectin in recipient mice failed to rescue lung function. LRA-mediated injury was localized to the transplanted lung and dependent on IL-1ß-mediated permeabilization of pulmonary vascular endothelium, which allowed extravasation of antibodies. Genetic deletion or pharmacological inhibition of IL-1R in the donor lungs prevented LRA-induced graft injury. In humans, preexisting LRAs were an independent risk factor for severe PGD and could be treated with plasmapheresis and complement blockade. We conclude that preexisting LRAs can compound ischemia-reperfusion injury to worsen PGD for which complement inhibition may be effective.

Ergonomics Workshop Improves Musculoskeletal Symptoms in General Surgery Residents.

INTRODUCTION: Poor operative ergonomics can lead to muscle fatigue and injury. However, formal ergonomics education is uncommon in surgical residencies. Our study examines the prevalence of musculoskeletal (MSK) symptoms, baseline ergonomics knowledge, and the impact of an ergonomics workshop in general surgery residents. METHODS: An anonymous voluntary presurvey and postsurvey was distributed to all general surgery residents at a single academic residency, assessing resident characteristics, MSK symptoms, and ergonomic knowledge before and after an ergonomics workshop. The workshop consisted of a lecture and a personalized posture coaching session with a physiatrist. RESULTS: The presurvey received 33/35 (94%) responses. Of respondents, 100% reported some degree of MSK pain. Prevalence of muscle stiffness and fatigue decreased with increasing height. Females reported higher frequencies of MSK pain (P = 0.01) and more muscle fatigue than males (100% versus 73%, P = 0.03). All residents reported little to no ergonomics knowledge with 68% reporting that ergonomics was rarely discussed in the operating room. The postsurvey received 26/35 (74%) responses. Of respondents, 100% reported the workshop was an effective method of ergonomics education. MSK symptom severity improved in 82% of residents. Reports that ergonomics was rarely discussed in the operating room significantly decreased to 22.8% of residents (P < 0.01). CONCLUSIONS: Surgical resident ergonomics knowledge is poor and MSK symptoms are common. Resident characteristics are associated with different MSK symptoms. Didactic teaching and personalized posture coaching improve ergonomics knowledge and reduce MSK symptom severity. Surgical residencies should consider implementing similar interventions to improve resident wellbeing.

Crosstalk between nonclassical monocytes and alveolar macrophages mediates transplant ischemia-reperfusion injury through classical monocyte recruitment.

Primary graft dysfunction (PGD) is the predominant cause of early graft loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular nonclassical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical monocytes (CM) permeabilize the vascular endothelium to allow neutrophil extravasation necessary for PGD. Here, we show that a CCL2-CCR2 axis is necessary for CM recruitment. Surprisingly, although intravital imaging and multichannel flow cytometry revealed that depletion of donor NCM abrogated CM recruitment, single cell RNA sequencing identified donor alveolar macrophages (AM) as predominant CCL2 secretors. Unbiased transcriptomic analysis of murine tissues combined with murine KOs and chimeras indicated that IL-1ß production by donor NCM was responsible for the early activation of AM and CCL2 release. IL-1ß production by NCM was NLRP3 inflammasome dependent and inhibited by treatment with a clinically approved sulphonylurea. Production of CCL2 in the donor AM occurred through IL-1R-dependent activation of the PKC and NF-κB pathway. Accordingly, we show that IL-1ß-dependent paracrine interaction between donor NCM and AM leads to recruitment of recipient CM necessary for PGD. Since depletion of donor NCM, IL-1ß, or IL-1R antagonism and inflammasome inhibition abrogated recruitment of CM and PGD and are feasible using FDA-approved compounds, our findings may have potential for clinical translation.

Comparative Effectiveness of Surgical Approaches for Lung Cancer.

BACKGROUND: The magnitude of association and quality of evidence comparing surgical approaches for lung cancer resection has not been analyzed. This has resulted in conflicting information regarding the relative superiority of the different approaches and disparate opinions on the optimal surgical treatment. We reviewed and systematically analyzed all published data comparing near- (30-d) and long-term mortality for minimally invasive to open surgical approaches for lung cancer. METHODS: Comprehensive search of EMBASE, MEDLINE, and the Cochrane Library, from January 2009 to August 2019, was performed to identify the studies and those that passed bias assessment were included in the analysis utilizing propensity score matching techniques. Meta-analysis was performed using random-effects and fixed-effects models. Risk of bias was assessed via the Newcastle-Ottawa Scale and the ROBINS-I tool. The study was registered in PROSPERO (CRD42020150923) prior to analysis. RESULTS: Overall, 1382 publications were identified but 19 studies were included encompassing 47,054 patients after matching. Minimally invasive techniques were found to be superior with respect to near-term mortality in early and advanced-stage lung cancer (risk ratio 0.45, 95% confidence interval [CI] 0.21-0.95, I2 = 0%) as well as for elderly patients (odds ratio 0.45, 95% CI 0.31-0.65, I2 = 30%), but did not demonstrate benefit for high-risk patients (odds ratio 0.74, 95% CI 0.06-8.73, I2 = 78%). However, no difference was found in long-term survival. CONCLUSIONS: We performed the first systematic review and meta-analysis to compare surgical approaches for lung cancer which indicated that minimally invasive techniques may be superior to thoracotomy in near-term mortality, but there is no difference in long-term outcomes.