Blood Flow Dynamics in a Giant Left Atrial Appendage Aneurysm Visualized by 4D-Flow CMR.

Aneurysms of the left atrial appendage (LAA) are rare entities that often require surgical intervention. We demonstrate multimodality imaging features of a giant LAA aneurysm, with a focus on 3-dimensional blood flow dynamics by using 4-dimensional-flow cardiac magnetic resonance. (Level of Difficulty: Advanced.).

Fulminant myocarditis in a patient with coronavirus disease 2019 and rapid myocardial recovery following treatment.

Coronavirus disease 2019 (COVID-19) is a global pandemic increasingly encountered in the clinical setting. It typically manifests as a respiratory illness, although cardiac involvement is common and portends a worse prognosis. We present the case of a 56-year-old male admitted with COVID-19 fulminant myocarditis and cardiogenic shock. We discuss important aspects of the multidisciplinary and interventional care involved in treating cardiogenic shock as well as the likely mechanisms of, and potential treatment for, COVID-19 myocarditis. The various pathways of myocardial injury, including direct viral damage, macrophage activation, and lymphocytic infiltration, are outlined in detail in addition to associated pathology such as cytokine release syndrome. COVID-19 is a complex and multisystem disease process; in addition to supportive care, specific consideration should be given to the underlying mechanism of injury for each patient.

Robotic-Assisted Thoracoscopic Repair of Right-Sided Bochdalek Hernia in Adults: A Two-Case Series.

Bochdalek hernia is a congenital diaphragmatic hernia that presents rarely in adulthood. Because of the paucity of cases, no standard repair technique has been identified. Here we present two cases of robotic, thoracoscopic repair of this rare hernia defect. Two separate adult patients with right-sided abdominal pain presented to the emergency department for evaluation. Both patients were diagnosed with right-sided Bochdalek hernia and repair was undertaken with a robotic, transthoracic approach. Repair technique is described in detail, including port placement, dissection technique, and repair strategy. Advantages of the robotic, transthoracic approach are discussed in detail. A transthoracic minimally invasive approach using a robotic platform is noted to be both feasible and practical in the treatment of adult Bochdalek hernia.

Thoracic Surgery Considerations in the Mentally Ill or Handicapped Patient.

Increasing prevalence of mentally ill and handicapped populations requiring surgical thoracic interventions has brought to light their worse associated morbidity and mortality. Baseline functional status, caretaker environment, and mental limitations in day to day life have an impact in the short and long term from these interventions. Aggressive perioperative care, multispecialty approach, technical aspects, palliative procedures, and ethical considerations all play a part in improving outcomes. In this article real cases are presented illustrating points of care and situations for discussion.

Post-operative morbidity, but not mortality, is worsened by operative delay in septic diverticulitis.

PURPOSE: Optimal timing of surgery for acute diverticulitis remains unclear. A non-operative approach followed by elective surgery 6-week post-resolution is favored. However, a subset of patients fail on the non-operative management during index admission. Here, we examine patients requiring emergent operation to evaluate the effect of surgical delay on patient outcomes. METHODS: Patients undergoing emergent operative intervention for acute diverticulitis were queried using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2005 to 2012. Primary endpoints of 30-day overall morbidity and mortality were evaluated via univariate and multivariate analysis. RESULTS: Of the 2,119 patients identified for study inclusion, 57.2 % (n = 1212) underwent emergent operative intervention within 24 h, 26.3 % (n = 558) between days 1-3, 12.9 % (n = 273) between days 3-7, and 3.6 % (n = 76) greater than 7 days from admission. End colostomy was performed in 77.4 % (n = 1,640) of cases. Unadjusted age and presence of major comorbidities increased with operative delay. Further, unadjusted 30-day overall morbidity, mortality, septic complications, and post-operative length of stay increased significantly with operative delay. On multivariate analysis, operative delay was not associated with increased 30-day mortality but was associated with increased 30-day overall morbidity. CONCLUSIONS: Hartmann's procedure has remained the standard operation in emergent surgical management of acute diverticulitis. Delay in definitive surgical therapy greater than 24 h from admission is associated with higher rates of morbidity and protracted post-operative length of stay, but there is no increase in 30-day mortality. Prospective study is necessary to further answer the question of surgical timing in acute diverticulitis.

Obstructing ventral hernias are not independently associated with surgical site infections.

BACKGROUND: Delayed operative intervention in the setting of adhesive bowel obstruction has been recently shown to increase the rate of surgical site infection (SSI), raising the concern for bacterial translocation. The effect of obstruction on SSI rate in patients with ventral hernia is unknown. The aim of this study was to assess the association between bowel obstruction and SSI in patients undergoing ventral hernia repair (VHR). MATERIALS AND METHODS: This study is a retrospective database review. Patients undergoing isolated VHR from 2005-2011 were identified from the American College of Surgeons' National Surgical Quality Improvement Program database. Demographics, comorbidities, and 30-d outcomes were analyzed. Multivariate logistic regression was used for variables with a P value of <0.1. RESULTS: A total of 68,811 patients underwent isolated VHR; 53.1% were male with mean age of 53 ± 15 y and body mass index of 32 ± 8. Hernia-related obstruction was found in 17,058 (24.8%). In patients with obstruction, SSI was more frequent (3.2% versus 2.6%, P < 0.001). Obesity, advanced age, vascular, pulmonary, hepatic, renal disease, and diabetes were more prevalent. After controlling for confounding baseline variables, bowel obstruction was not independently associated with SSI (odds ratio, 0.983, 95% confidence interval, 0.872-1.107). Subgroup analysis of clean classified cases also demonstrated the lack of independent association between obstruction and SSI. CONCLUSIONS: Obstruction in patients undergoing VHR is not independently associated with SSI. Our results suggest that mesh implantation remains a viable option in this setting. Other confounding comorbid conditions should be assessed at the time of surgical intervention to identify patients appropriate for mesh repair.

Bariatric Surgery in Patients with Dialysis-Dependent Renal Failure.

BACKGROUND: Laparoscopic procedures for the treatment of morbid obesity are commonly offered to patients with comorbidities previously thought to carry prohibitive operative risk. In this study, we reviewed characteristics and perioperative outcomes of patients with dialysis-dependent renal failure (DDRF) who underwent laparoscopic bariatric procedures. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2006 to 2011 was reviewed. Preoperative characteristics and 30-day outcome data of patients who underwent three common laparoscopic procedures were analyzed using ANOVA and Pearson chi-squared tests. RESULTS: One hundred thirty-eight patients (52.5 % female) with DDRF and a median body mass index (BMI) of 45.5 kg/m(2) were identified; 33.8 % (n = 47) underwent laparoscopic banding (LAGB), 48.9 % (n = 68) laparoscopic Roux-en-Y gastric bypass (RYGB), and 16.5 % (n = 23) laparoscopic sleeve gastrectomy (LSG). No differences were found among groups in age, prevalence of American Society of Anesthesiology IV classification, BMI, weight, gender, prevalence of diabetes, and vascular or neurologic comorbidities. Total operation time and length of hospital stay were significantly different between groups. Mortality was 0.7 %, and overall morbidity was 5.8 %. The case mix reflected a decrease in LAGB procedures from 45.5 to 23.3 % from 2006-2009 to 2010-2011 and an increase in LSG procedures from 9.1 to 24.7 % (p < 0.006). CONCLUSIONS: When performed in selected DDRF patients, bariatric surgery is safe. An increase in LSG with a concurrent decline in LAGB procedures was demonstrated over the period of the study.

Synchronous Ventral Hernia Repair in Patients Undergoing Bariatric Surgery.

BACKGROUND: Obesity predisposes patients to abdominal wall hernias. Patients undergoing bariatric surgery are not uncommonly found to have ventral hernias. Synchronous ventral hernia repair (S-VHR) has been reported in 2-5% of patients undergoing bariatric surgery. Studies reporting on the outcomes of S-VHR are limited by sample size. The aim of this study was to assess the effect of S-VHR on surgical site infection (SSI) rate. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2010 to 2011 was queried using Current Procedural Terminology codes for bariatric surgery. Data on patient demographics, comorbidities, procedural events, and postoperative occurrences were analyzed. Thirty-day mortality and morbidity were assessed. Comparisons between laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were performed. RESULTS: We identified 17,117 patients who underwent RYGB or SG. S-VHR was performed in 503 (2.94%) patients. S-VHR was independently associated with SSI (odds ratios (OR) 1.65, 95% confidence interval (CI) 1.06-2.58), but not overall morbidity (OR 1.33, 95% CI 0.96-1.86). Four hundred thirty-three patients with RYGB and 70 with SG had S-VHR. Serious morbidity (3.5 vs. 5.7%, p = 0.32) and overall morbidity (8.3 vs. 8.6%, p = 0.942) were similar. After controlling for baseline comorbidities, there was no significant effect of procedure type on SSI (OR 0.38, 95% CI 0.05-2.91). CONCLUSIONS: S-VHR is associated with an increase in SSI but not overall morbidity. There is no significant difference in the SSI rate between RYGB and SG. Larger studies are needed to definitively assess a potential difference in the wound infection rate between RYGB and SG.

N-nitroso-tris-chloroethylurea induces premalignant squamous dysplasia in mice.

Squamous cell carcinoma (SCC) and premalignant endobronchial lesions have been difficult to study in murine models. In this study, we evaluate the topical N-nitroso-tris-chloroethylurea (NTCU) murine SCC model, determine the extent to which resulting premalignant airway dysplasia develops, discuss clinicopathologic grading criteria in lesion progression, and confirm that immunohistochemical (IHC) staining patterns are consistent with those observed in human endobronchial dysplasia and SCC. Male and female FVB mice were treated biweekly with topical NTCU (4, 8, or 40 mmol/L) or vehicle for 32 weeks. Following sacrifice, squamous cell lesions were enumerated and categorized into the following groups: flat atypia, low-grade dysplasia, high-grade dysplasia, and invasive SCC. The 40 mmol/L NTCU concentration produced the entire spectrum of premalignant dysplasias and squamous cell carcinomas, but was associated with poor survival. Concentrations of 4 and 8 mmol/L NTCU were better tolerated and produced only significant levels of flat atypia. Squamous origin of the range of observed lesions was confirmed with IHC staining for cytokeratin 5/6, p63, thyroid transcription factor-1 (TTF-1), and Napsin-A. This study shows that topical application of high-dose NTCU produces endobronchial premalignant lesions with classic squamous characteristics and should allow for improved preclinical evaluation of potential chemopreventive agents.

Spinal microvascular expression of PV-1 is associated with inflammation, perivascular astrocyte loss, and diminished EC glucose transport potential in acute SCI.

The endothelial-specific expression of plasmalemmal vesicle associated protein-1 (PV-1) is typical of fenestrated endothelium observed in pulmonary capillaries and some endocrine organs. In the central nervous system (CNS) it is expressed during development but disappears concomitant with maturation of the blood-CNS barrier [1]. Consistent with observations made in models of stroke, Alzheimer's disease, and tumorigenesis, we show PV-1 expression in the spinal cord specifically upregulated by pathologically-activated endothelial cells (ECs) in response to traumatic spinal cord injury (SCI). Adult female C57Bl/6 mice received a moderate T9/10 contusive SCI. PV-1 assessed by qRT-PCR and immunohistochemistry 3 hours to 14 days post-injury showed expression as early as 1 day post-SCI, with levels decreasing by 14 days. This expression was associated with microvessels in the injury epicenter and penumbral zone, with the time course and distribution correlated with progressing peripheral inflammatory cell infiltration. PV-1-immunoreactive ECs were angiogenic as demonstrated by intravascular binding of Griffonia simplicifolia isolectin B4 (IB4). ECs expressing high levels of PV-1 were anatomically and physiologically abnormal with altered/absent immunostaining for occludin and zonula occludens-1 (ZO-1), and decreased expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4). Glucose transporter type I (Glut-1) expression decreased in affected, PV-1 positive microvessels with little colocalization of PV-1 and Glut-1 apparent by 7 days post-SCI. These data suggest that upregulation of microvascular expression of PV-1 post-SCI may promote major components of secondary injury including extravasation of cellular and acellular mediators of inflammation and may accelerate loss of neuropil and decline in the functional and anatomical integrity of the neurovascular unit (NVU).

Chemoprevention of murine lung cancer by gefitinib in combination with prostacyclin synthase overexpression.

INTRODUCTION: We hypothesized that the combination of the EGFR tyrosine kinase inhibitor (TKI) gefitinib with the powerful chemopreventive manipulation of lung-specific transgenic prostacyclin synthase (PGIS) overexpression on tumorigenesis in FVB/N mice would result in augmented chemoprevention. MATERIALS AND METHODS: Wildtype and littermate PGIS overexpressors (OE) were given urethane, 1 mg/kg i.p. followed by thrice weekly i.p. injections of gefitinib, 50 mg/kg or 100 mg/kg, or vehicle. Pulmonary adenomas were enumerated and measured. RESULTS: Gefitinib at either 50 mg/kg or 100 mg/kg administered i.p. three times weekly was effective in inhibiting EGF induced EGFR tyrosine phosphorylation and downstream signaling. The PGIS overexpressors showed significant decreases in tumor multiplicity consistent with prior studies. Gefitinib had no effect on tumor multiplicity or volume in wildtype mice. Among the PGIS overexpressors, a significant reduction in tumor multiplicity was shown in the 50 mg/kg, but not the 100 mg/kg, gefitinib treatment group vs. vehicle control animals (1.13+/-0.29 vs. 2.29+/-0.32 tumors/mouse, p=0.015). We examined the phosphorylation status in selected downstream effectors of EGFR (Erk, Akt, Src, PTEN). The major difference in the 50 mg/kg vs. 100 mg/kg group was an increase in p-Src in the PGIS OE mice receiving the higher dose. CONCLUSION: We conclude that gefitinib alone has no chemopreventive efficacy in this model; it augmented the effect of PGIS overexpression at 50 mg/kg but not 100 mg/kg. Increased p-Src is correlated with loss of efficacy at the higher dose, suggesting the potential for combined EGFR and Src inhibition strategies in chemoprevention.

Prostacyclin prevents murine lung cancer independent of the membrane receptor by activation of peroxisomal proliferator--activated receptor gamma.

Overexpression of prostacyclin synthase (PGIS) decreases lung tumor multiplicity in chemical- and cigarette-smoke-induced murine lung cancer models. Prostacyclin signals through a single G-protein-coupled receptor (IP), which signals through cyclic AMP. To determine the role of this receptor in lung cancer chemoprevention by prostacyclin, PGIS-overexpressing mice were crossed to mice that lack the IP receptor [IP(-/-)]. Carcinogen-induced lung tumor incidence was similar in IP(+/+), IP(+/-), and IP(-/-) mice, and overexpression of PGIS gave equal protection in all three groups, indicating that the protective effects of prostacyclin are not mediated through activation of IP. Because prostacyclin can activate members of the peroxisomal proliferator-activated receptor (PPAR) family of nuclear receptors, we examined the role of PPARgamma in the protection of prostacyclin against lung tumorigenesis. Iloprost, a stable prostacyclin analogue, activated PPARgamma in nontransformed bronchial epithelial cells and in a subset of human non-small-cell lung cancer cell lines. Iloprost-impregnated chow fed to wild-type mice resulted in elevated lung macrophages and decreased lung tumor formation. Transgenic animals with lung-specific PPARgamma overexpression also developed fewer lung tumors. This reduction was not enhanced by administration of supplemental iloprost. These studies indicate that PPARgamma is a critical target for prostacyclin-mediated lung cancer chemoprevention and may also have therapeutic activity.