Preoperative intervention for smoking cessation: A systematic review.

BACKGROUND: Smoking is associated with increased postoperative complications. Pre-surgical smoking cessation remains a challenge. Our aim was to summarize pre-hospital smoking cessation interventions and impact on smoking cessation rates. METHODS: Independent review of English language articles identified from systematic searches of MEDLINE, PubMed, PsycInfo, Embase, Web of Science, and Cumulative Index to Nursing & Allied Health Literature databases from 1998 to 2019 was performed (PROSPERO registration number CRD42021247927). Studies of adult patients enrolled in a pre-hospital smoking cessation intervention were included. Studies with historical controls or only self-reported outcomes were excluded. RESULTS: Nine articles including 1762 patients were identified. Exhaled CO was used to confirm cessation. Six studies reported smoking status day of surgery. Interventions included NRT, hand-held technology, e-cigarettes, decision aids/counseling and medications. Four studies demonstrated a difference in smoking cessation rates. Ethics and study appraisal were assessed using ROB2. CONCLUSIONS: Based on the variability of interventions, settings, and outcomes, best practice for successful pre-hospital smoking cessation in surgery clinics would benefit from ongoing investigation.

Revisional Surgery in Patients with Recurrent Dysphagia after Heller Myotomy.

BACKGROUND: Recurrent/persistent symptoms of achalasia occur in 10-20% of individuals after Heller myotomy. The causes and treatment outcomes are ambiguous. Our aim is to assess the causes and outcomes of a multidisciplinary approach to this patient population. METHODS: All patients undergoing revisional operations after a Heller myotomy were reviewed retrospectively. DATA COLLECTED: demographics, date of initial Heller myotomy, preoperative evaluation, etiology of recurrent symptoms, date of revisional operation, and surgical outcomes. RESULTS: A total of 34 patients underwent 37 revisional operations. Operations were tailored based on preoperative multidisciplinary evaluation. Causes of symptoms: periesophageal/perihiatal fibrosis 11 (27%), obstructing fundoplication 11 (27%), incomplete myotomy 8 (20%), progression of disease 9 (22%), and epiphrenic diverticulum 1 (2%). Operations performed: reversal/no creation of fundoplication with or without re-do myotomy 22 (59%), revision/creation of fundoplication with or without myotomy 6 (16%), and esophagectomy 9 (24%). Ten patients in the 37 operations (27%) developed postoperative complications. Of 33 patients for 36 operations with follow-up, 25 patient-operations (69%) resulted in resolution or improved dysphagia. Although there was variation in symptomatic improvement by cause and operation type, none reached statistical significance. CONCLUSION: There are several causes of dysphagia after Heller myotomy and a thoughtful evaluation is required. Complication rates are higher than first-time operations. Symptomatic improvement occurs in the majority of cases, but a significant minority will have persistent dysphagia. Although an individualized approach to dysphagia after Heller myotomy may improve symptoms and passage of food, the perception of dysphagia may persist in patients.

Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.

Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A growing body of evidence supports a strong link between neovascular disease and inflammation. Metabolites of long-chain polyunsaturated fatty acids derived from the cytochrome P450 (CYP) monooxygenase pathway serve as vital second messengers that regulate a number of hormones and growth factors involved in inflammation and vascular function. Using transgenic mice with altered CYP lipid biosynthetic pathways in a mouse model of laser-induced CNV, we characterized the role of these lipid metabolites in regulating neovascular disease. We discovered that the CYP-derived lipid metabolites epoxydocosapentaenoic acids (EDPs) and epoxyeicosatetraenoic acids (EEQs) are vital in dampening CNV severity. Specifically, overexpression of the monooxygenase CYP2C8 or genetic ablation or inhibition of the soluble epoxide hydrolase (sEH) enzyme led to increased levels of EDP and EEQ with attenuated CNV development. In contrast, when we promoted the degradation of these CYP-derived metabolites by transgenic overexpression of sEH, the protective effect against CNV was lost. We found that these molecules work in part through their ability to regulate the expression of key leukocyte adhesion molecules, on both leukocytes and endothelial cells, thereby mediating leukocyte recruitment. These results suggest that CYP lipid signaling molecules and their regulators are potential therapeutic targets in neovascular diseases.

The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy.

Proliferative retinopathic diseases often progress in 2 phases: initial regression of retinal vasculature (phase 1) followed by subsequent neovascularization (NV) (phase 2). The immune system has been shown to aid in vascular pruning in such retinopathies; however, little is known about the role of the alternative complement pathway in the initial vascular regression phase. Using a mouse model of oxygen-induced retinopathy (OIR), we observed that alternative complement pathway-deficient mice (Fb(-/-)) exhibited a mild decrease in vascular loss at postnatal day (P)8 compared with age- and strain-matched controls (P = 0.035). Laser capture microdissection was used to isolate the retinal blood vessels. Expression of the complement inhibitors Cd55 and Cd59 was significantly decreased in blood vessels isolated from hyperoxic retinas compared with those from normoxic control mice. Vegf expression was measured at P8 and found to be significantly lower in OIR mice than in normoxic control mice (P = 0.0048). Further examination of specific Vegf isoform expression revealed a significant decrease in Vegf120 (P = 0.00032) and Vegf188 (P = 0.0092). In conjunction with the major modulating effects of Vegf during early retinal vascular development, our data suggest a modest involvement of the alternative complement pathway in targeting vessels for regression in the initial vaso-obliteration stage of OIR.

Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury.

Degeneration of photoreceptors is a primary cause of vision loss worldwide, making the underlying mechanisms surrounding photoreceptor cell death critical to developing new treatment strategies. Retinal detachment, characterized by the separation of photoreceptors from the underlying retinal pigment epithelium, is a sight-threatening event that can happen in a number of retinal diseases. The detached photoreceptors undergo apoptosis and programmed necrosis. Given that photoreceptors are nondividing cells, their loss leads to irreversible visual impairment even after successful retinal reattachment surgery. To better understand the underlying disease mechanisms, we analyzed innate immune system regulators in the vitreous of human patients with retinal detachment and correlated the results with findings in a mouse model of retinal detachment. We identified the alternative complement pathway as promoting early photoreceptor cell death during retinal detachment. Photoreceptors down-regulate membrane-bound inhibitors of complement, allowing for selective targeting by the alternative complement pathway. When photoreceptors in the detached retina were removed from the primary source of oxygen and nutrients (choroidal vascular bed), the retina became hypoxic, leading to an up-regulation of complement factor B, a key mediator of the alternative pathway. Inhibition of the alternative complement pathway in knockout mice or through pharmacological means ameliorated photoreceptor cell death during retinal detachment. Our current study begins to outline the mechanism by which the alternative complement pathway facilitates photoreceptor cell death in the damaged retina.

Characterization of a spontaneous retinal neovascular mouse model.

BACKGROUND: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. METHODS: The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. RESULTS: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. CONCLUSIONS: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.