IL-33 mediates Pseudomonas induced airway fibrogenesis and is associated with CLAD.

BACKGROUND: Long term outcomes of lung transplantation are impacted by the occurrence of chronic lung allograft dysfunction (CLAD). Recent evidence suggests a role for the lung microbiome in the occurrence of CLAD, but the exact mechanisms are not well defined. We hypothesize that the lung microbiome inhibits epithelial autophagic clearance of pro-fibrotic proteins in an IL-33 dependent manner, thereby augmenting fibrogenesis and risk for CLAD. METHODS: Autopsy derived CLAD and non-CLAD lungs were collected. IL-33, P62 and LC3 immunofluorescence was performed and assessed using confocal microscopy. Pseudomonas aeruginosa (PsA), Streptococcus Pneumoniae (SP), Prevotella Melaninogenica (PM), recombinant IL-33 or PsA-lipopolysaccharide was co-cultured with primary human bronchial epithelial cells (PBEC) and lung fibroblasts in the presence or absence of IL-33 blockade. Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate IL-33 expression, autophagy, cytokines and fibroblast differentiation markers. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of Beclin-1. RESULTS: Human CLAD lungs demonstrated markedly increased expression of IL-33 and reduced basal autophagy compared to non-CLAD lungs. Exposure of co-cultured PBECs to PsA, SP induced IL-33, and inhibited PBEC autophagy, while PM elicited no significant response. Further, PsA exposure increased myofibroblast differentiation and collagen formation. IL-33 blockade in these co-cultures recovered Beclin-1, cellular autophagy and attenuated myofibroblast activation in a Beclin-1 dependent manner. CONCLUSION: CLAD is associated with increased airway IL-33 expression and reduced basal autophagy. PsA induces a fibrogenic response by inhibiting airway epithelial autophagy in an IL-33 dependent manner.

All-cause Readmission after Transcatheter Aortic Valve Replacement in a Community Hospital - Long Term Follow-up.

BACKGROUND: Post-procedure readmissions are associated with lower quality of life and increased economic burden. The study aimed to identify predictors for long-term all-cause readmissions in patients who underwent transcatheter aortic valve replacement (TAVR) in a community hospital. METHODS: A Historical cohort study of all adults who underwent TAVR at Cape-Cod hospital between June 2015 and December 2017 was performed and data on readmissions was collected up-to May 2020 (median follow up of 3.3 years). Pre-procedure, procedure and in-hospital post-procedure parameters were collected. Readmission rate was evaluated, and univariate and multivariable analyses were applied to identify predictors for readmission. RESULTS: The study included 262 patients (mean age 83.7±7.9 years, 59.9% males). The median Society of Thoracic Surgeons (STS) probability of mortality (PROM) score was 4.9 (IQR, 3.1-7.9). Overall, 120 patients were readmitted. Ten percent were readmitted within 1-month, 20.8% within 3-months, 32.0% within 6-months and 44.5% within 1-year. New readmissions after 1-year were rare. STS PROM 5% or above (HR 1.50, p = 0.039), pre-procedure anemia (HR 1.63, p = 0.034), severely decreased pre-procedure renal function (HR 1.93, p = 0.040) and procedural complication (HR 1.65, p = 0.013) were independent predictors for all-cause readmission. CONCLUSIONS: Elevated procedural risk, anemia, renal dysfunction and procedural complication are important predictors for readmission. Pre-procedure and ongoing treatment of the patient's background diseases and completion of treatment for complications prior to discharge may contribute to a reduction in the rate of readmissions.

Advanced Surgical and Percutaneous Approaches to Pulmonary Vascular Disease.

Despite progress in modern medical therapy, pulmonary hypertension remains an unremitting disease. Once severe or refractory to medical therapy, advanced percutaneous and surgical interventions can palliate right ventricular overload, bridge to transplantation, and overall extend a patient's course. These approaches include atrial septostomy, Potts shunt, and extracorporeal life support. Bilateral lung transplantation is the ultimate treatment for eligible patients, although the need for suitable lungs continues to outpace availability. Measures such as ex vivo lung perfusion are ongoing to expand donor lung availability, increase rates of transplant, and decrease waitlist mortality.

Left ventricle unloading strategies in ECMO: A single-center experience.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking. MATERIALS & METHODS: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications. RESULTS: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%). DISCUSSION: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design.

Operative Techniques and Pitfalls in Donor Bilateral Lung Procurement.

BACKGROUND: Demand for lung transplant continues to grow nationally, and the number of donation after brain death and donation after circulatory death lung procurements increases each year. METHODS: We describe the Stanford technique for bilateral lung procurement for donation after brain death and donation after circulatory death and highlight the pitfalls and common mistakes to standardize the procurement process and ensure proper harvesting to prevent organ loss. RESULTS: Damage to the lung graft during bilateral en bloc procurement most commonly results from either poor preservation or injury to a pulmonary vein during division of the left atrial cuff. CONCLUSION: En bloc bilateral lung procurement should be standardized to ensure reproducible graft harvesting and preservation while teaching new generations of transplant surgeons.

Use of Historical Surgical Times to Predict Duration of Primary Aortic Valve Replacement.

OBJECTIVES: To test whether a model using a historical average of a surgeon's surgical times for primary aortic valve replacements is a more accurate predictor of actual surgical times than solely relying on a surgeon's estimate. DESIGN: Retrospective review. SETTING: Single university hospital that serves as a tertiary referral center. PARTICIPANTS: All patients undergoing primary aortic valve replacement between October 2008 and September 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Estimation biases, calculated as the difference between actual and predicted surgical time, were compared between the surgeon and the model, which included between 2 and 20 cases in the historical average. Kruskal-Wallis analysis of variance was used to compare all values. Pairwise comparisons were made using the Steel-Dwass test to determine whether using more cases in the model resulted in smaller estimation biases. Using the historical model reduced mean overestimation bias from 55.30 minutes to 0.90-to-4.67 minutes. No significant difference was seen based on the number of cases used. CONCLUSIONS: An uncomplicated model can assist in providing comparatively unbiased estimations of surgical time for aortic valve replacements. The model can rely on a fewer number of cases (eg, 5) and does not benefit from including more cases (eg, 20).

Rapidly Expanding Infectious Aortic Aneurysm Caused by Perforated Colon Cancer.

A 50-year-old male smoker presented with a perforated colon cancer and underwent an extended right colectomy. Feculent peritonitis was treated with empiric antibiotics. Postoperatively he developed severe back pain and rising leukocytosis. Serial computed tomography revealed a rapidly expanding infrarenal aortic aneurysm. He was urgently treated with extra-anatomic bypasses and aortic resection. No organisms grew from the resected aortic wall. He was discharged in stable condition, and the ileostomy was reversed 9 months later.

A subjective assessment of medical student perceptions on animal models in medical education.

BACKGROUND: There remains increasing societal pressure to limit the use of animals in medical education. The purpose of this study was to explore the subjective perceptions that medical students exposed to an animal model curriculum feel about the laboratory and its continued use. METHODS: A 6-month prospective study was performed during the medical college core surgical clerkship. Medical students participated in both a trainer-based simulation workshop (dry laboratory) and a live-tissue animal laboratory (wet laboratory) in addition to their operative experience. Students completed a 23-question Likert survey at the end of the surgical clerkship. Data were compared using the chi-square test. RESULTS: More students reported increased subjective stress levels in the wet laboratory (32.4%) compared with the dry laboratory (5.4%, p < 0.001). In addition, more students felt the wet laboratory (vs dry laboratory) prepared them for the anxiety (55.4% vs 24.3%, p < 0.001) and technical demands (67.6% vs 44.6%, p = 0.005) of the operating room. The majority of medical students (>90%) felt the wet laboratory was an important experience and should be continued. CONCLUSIONS: The results of this study show a subjective benefit perceived by medical students when it comes to participation in an animal laboratory during their surgical clerkship. As such, over 90% of participating medical students feel the animal laboratory is important in medical education and should be continued in their surgical curriculum.

Higher clinical performance during a surgical clerkship is independently associated with matriculation of medical students into general surgery.

BACKGROUND: The purpose of our study was to determine the predictive impact of individual academic measures for the matriculation of senior medical students into a general surgery residency. METHODS: Academic records were evaluated for third-year medical students (n = 781) at a single institution between 2004 and 2011. Cohorts were defined by student matriculation into either a general surgery residency program (n = 58) or a non-general surgery residency program (n = 723). Multivariate logistic regression was performed to evaluate independently significant academic measures. RESULTS: Clinical evaluation raw scores were predictive of general surgery matriculation (P = .014). In addition, multivariate modeling showed lower United States Medical Licensing Examination Step 1 scores to be independently associated with matriculation into general surgery (P = .007). CONCLUSIONS: Superior clinical aptitude is independently associated with general surgical matriculation. This is in contrast to the negative correlation United States Medical Licensing Examination Step 1 scores have on general surgery matriculation. Recognizing this, surgical clerkship directors can offer opportunities for continued surgical education to students showing high clinical aptitude, increasing their likelihood of surgical matriculation.