Management of aortoesophageal fistula primarily using esophageal preservation.

Objective: Aortoesophageal fistula is a rare, life-threatening condition. There is no consensus regarding the surgical management of the esophagus in this condition. Methods: We retrospectively evaluated 13 patients diagnosed with aortoesophageal fistulas at a single institution from 2003 to 2021. Descriptive statistics were used to analyze patient characteristics, operative characteristics, and patient outcomes. Kaplan-Meier survival analysis was performed. Results: Patients' mean age was 63.5 years, and 6 (46.2%) were female. The most common presenting symptoms were hemoptysis/hematemesis (69.2%), chest/back pain (46.2%), and fever (38.5%). Twelve patients (92.3%) had a history of aortic procedures. The median time between the index operation and repair of the secondary aortoesophageal fistula in the 12 patients was 5 months. The index operation was a thoracic endovascular aortic repair in 10 of 12 patients (83.3%). Eleven patients (84.6%) underwent primary esophageal repair with flap coverage (omentum or muscle). One of these patients needed an esophagectomy within 1 year. The primary surgical management of the aorta was graft excision and replacement, aside from 1 patient who underwent primary repair. The 30-day survival was 69.2%, and 1-year and 5-year survivals were 31.7%. There were no recurrent infections at the esophageal fistula site. Conclusions: Aortoesophageal fistula remains a rare condition, but its case numbers have increased with thoracic endovascular aortic repair. It continues to be a difficult condition to manage and has a high fatality rate. Esophageal-preserving surgery may be a safe and less-invasive option for patients with a small defect.

Functional Outcomes of Primary Arthrodesis (PA) Versus Open Reduction and Internal Fixation (ORIF) in the Treatment of Lisfranc Injuries.

OBJECTIVES: To determine whether primary arthrodesis (PA) or open reduction and internal fixation (ORIF) results in better functional outcomes through patient-reported outcome measures (PROMs). Reoperation rates and surgical characteristics among the 2 groups are evaluated as well. DESIGN: A retrospective cohort study. SETTING: Level 1 trauma center. PATIENTS: Eighty-one patients treated using PA or ORIF for Lisfranc injuries between January 2010 and January 2019. MAIN OUTCOME MEASUREMENTS: PROMs were collected using the validated Foot and Ankle Ability Measure questionnaire. Follow-up ranged from 1 to 10 years posttreatment. RESULTS: Two hundred patients underwent ORIF, and 72 patients underwent PA. Eighty-one of 272 patients responded to the questionnaire. The Foot and Ankle Ability Measure revealed activities of daily living subscores for PA and ORIF of 69.78 ± 18.61 and 73.53 ± 25.60, respectively ( P = 0.48). The Sports subscores for PA (45.81 ± 24.65) and ORIF (56.54 ± 31.13) were not significantly different ( P = 0.11). Perceived levels of activities of daily living ( P = 0.32) and Sports ( P = 0.81) function, compared with preinjury levels, were also not significantly different between the 2 groups. Rates of reoperation were nearly identical for PA (28.1%) and ORIF (30.6%) ( P = 1.00). CONCLUSION: Our results suggest that neither PA nor ORIF is superior regarding functional outcomes or rates of reoperation in the surgical treatment of Lisfranc injuries when appropriately triaged by the treating surgeon. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Avascular Necrosis of the Talus Following Subchondroplasty: A Case Report and Review of Literature.

CASE: Avascular necrosis (AVN) of the talus in a 45-year-old female following subchondroplasty with calcium phosphate bone filler for treatment of anterolateral and posteromedial talar dome bone marrow lesions (BMLs). The patient subsequently presented as consultation, 18 months postoperatively, with AVN of the talus. After failing conservative management, the patient underwent a total ankle arthroplasty at 46 months after subchondroplasty with resolution of pain. CONCLUSION: There are few studies that have reported on the safety of subchondroplasty of the talus. Given the tenuous blood supply to the talar body and poor patient outcomes associated with AVN, caution should be taken before extrapolating the generally positive results of subchondroplasty in the knee. LEVEL OF EVIDENCE: Level IV.

AIM2 Inflammasome Activation Contributes to Aortic Dissection in a Sporadic Aortic Disease Mouse Model.

BACKGROUND: The absent in melanoma 2 (AIM2) inflammasome induces pyroptosis, tissue inflammation, and extracellular matrix destruction. We tested the hypothesis that the AIM2 inflammasome contributes to aortic aneurysm and dissection (AAD) development by promoting pyroptosis in smooth muscle cells (SMCs). METHODS: We examined AIM2 expression in aortic tissues from patients with ascending thoracic aortic aneurysm (ATAA) and aortic dissection (ATAD) and from organ donor controls. AIM2's role in AAD development was evaluated in AIM2-deficient mice in a sporadic AAD model induced by challenging mice with a high-fat diet and angiotensin II infusion. The direct effects of dsDNA on SMC death in vitro were studied. RESULTS: Western blot analyses showed that AIM2 was increased in ATAD compared to ATAA and control tissue. Immunofluorescence demonstrated increased AIM2 in SMCs and macrophages in the aortic media and adventitia of dissected tissue. Increased AIM2 abundance was associated with increased cleavage of caspase-1 and cleavage of gasdermin-D, indicating activation of pyroptosis. In a mouse model of sporadic AAD induced by high-fat diet and angiotensin II infusion, AIM2-deficient mice showed significant reduction in aortic dissection, but not aneurysm formation in all aortic segments, versus wild-type mice. Finally, treating cultured human aortic SMCs with double-stranded DNA induced AIM2 expression, caspase-1 cleavage, and gasdermin-D cleavage; these effects were reduced by silencing AIM2 and caspase-1 genes, suggesting involvement of the AIM2 inflammasome in cytosolic DNA-induced activation of SMC pyroptosis. CONCLUSIONS: Activation of the AIM2 inflammasome cascade contributes to aortic degeneration and dissection, in part, by activating pyroptosis.

New Technologies With Increased Precision Improve Understanding of Endothelial Cell Heterogeneity in Cardiovascular Health and Disease.

Endothelial cells (ECs) are vital for blood vessel integrity and have roles in maintaining normal vascular function, healing after injury, and vascular dysfunction. Extensive phenotypic heterogeneity has been observed among ECs of different types of blood vessels in the normal and diseased vascular wall. Although ECs with different phenotypes can share common functions, each has unique features that may dictate a fine-tuned role in vascular health and disease. Recent studies performed with single-cell technology have generated powerful information that has significantly improved our understanding of EC biology. Here, we summarize a variety of EC types, states, and phenotypes recently identified by using new, increasingly precise techniques in transcriptome analysis.

Single-Cell Analysis of Aneurysmal Aortic Tissue in Patients with Marfan Syndrome Reveals Dysfunctional TGF-ß Signaling.

The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations of cell populations with increased de-differentiated proliferative SMCs compared to controls. Furthermore, there was a downregulation of MYOCD and MYH11 in SMCs, and an upregulation of COL1A1/2 in fibroblasts in MFS samples compared to controls. We also examined TGF-ß signaling, an important pathway in aortic homeostasis. We found that TGFB1 was significantly upregulated in two fibroblast clusters in MFS tissues. However, TGF-ß receptor genes (predominantly TGFBR2) and SMAD genes were downregulated in SMCs, fibroblasts, and ECs in MFS, indicating impairment in TGF-ß signaling. In conclusion, despite upregulation of TGFB1, the rest of the canonical TGF-ß pathway and mature SMCs were consistently downregulated in MFS, indicating a potential compromise of TGF-ß signaling and lack of stimulus for SMC differentiation.

Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues. METHODS: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies. RESULTS: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene(ERG) exerts an important role in maintaining normal aortic wall function. CONCLUSIONS: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.

Simultaneous Erb's and Klumpke's palsy: Case report.

Mapping nerve deficits during a physical exam after trauma to the upper extremity can help determine not only if the brachial plexus was injured but also which nerve roots were involved. A 28-year-old male presented with simultaneous signs and symptoms of Erb's (C5) and Klumpke's (C8, T1) palsy, with sparing of the C6 and C7 roots. The patient presented several months ago to his local emergency room with shortness of breath, which was determined to be caused by left diaphragmatic paralysis through clinical and radiographical evidence. However, the etiology of the current nerve dysfunction in the upper extremity remained unknown. With persistent questioning and establishing the patient's trust in the caregivers, it was revealed that the patient had attempted suicidal hanging. We describe the clinical features and the likely mechanism of injury leading to this previously unreported combination of brachial plexus injuries. The unique injuries to this patient's brachial plexus can be explained by the sequence of events during the attempted suicidal hanging. The upper brachial plexus was injured during the initial moments where the neck was excessively stretched and the lower brachial plexus was injured due to the patient reaching up and holding himself by his arm for an extended period of time.

Characterization of a novel two-partner secretion system in Escherichia coli O157:H7.

Gram-negative bacteria contain multiple secretion pathways that facilitate the translocation of proteins across the outer membrane. The two-partner secretion (TPS) system is composed of two essential components, a secreted exoprotein and a pore-forming beta barrel protein that is thought to transport the exoprotein across the outer membrane. A putative TPS system was previously described in the annotation of the genome of Escherichia coli O157:H7 strain EDL933. We found that the two components of this system, which we designate OtpA and OtpB, are not predicted to belong to either of the two major subtypes of TPS systems (hemolysins and adhesins) based on their sequences. Nevertheless, we obtained direct evidence that OtpA and OtpB constitute a bona fide TPS system. We found that secretion of OtpA into the extracellular environment in E. coli O157:H7 requires OtpB and that when OtpA was produced in an E. coli K-12 strain, its secretion was strictly dependent on the production of OtpB. Furthermore, using OtpA/OtpB as a model system, we show that protein secretion via the TPS pathway is extremely rapid.