Internal mammary artery perforator flap for repair of an upper thoracic tracheo-oesophageal fistula.

Tracheoesophageal fistulas (TOF) following esophagectomy for esophageal cancer are rare but potentially fatal. There is no consensus on treatment between stenting and surgical repair, although the latter is associated with better distant survival. In surgical repair, the interposition of a flap improves healing by providing well-vascularized tissue and reinforcing the repair zone. The flaps described are usually muscular and decaying. We present the case of a malnourished fifty-year-old man who underwent intrathoracic surgical repair of symptomatic recurrent TOF using a skin flap based on the perforators of the internal thoracic artery (IMAP). The perforator flap was completely de-epidermized and tunneled under the sternum by a proximal and limited resection of the 3rd costal cartilage and placed at the posterior aspect of the trachea, with the excess tissue rolled up on either side. At 9 months, the patient showed no recurrence and improved general condition. The de-epidermized IMAP tunneled under the sternum intrathoracically is a reliable alternative to the conventional muscle flaps described in TOF management and an attractive additional tool in the plastic surgeon's surgical arsenal.

Reconstruction of the anterior chest wall using the internal mammary artery perforator flap (IMAP): About a series of 23 cases.

BACKGROUND: The advent of propeller flaps has permitted new and less invasive coverage solutions for thoracic defects compared to conventional flaps. Through a retrospective analysis of our cases, we would like to show the advantages of the internal mammary artery perforator (IMAP) flap for anterior chest wall reconstruction. METHODS: We included patients who underwent anterior chest wall reconstruction with an IMAP propeller flap in the Toulouse University Hospital's plastic surgery department from January 2019 to December 2022. The data were collected on patient data, skin defects, and flap characteristics. RESULTS: Twenty-three IMAP flaps were realized to cover locoregional defects. The skin paddle size of the IMAP flap averaged 15.6cm long (12-20)×6.7cm wide (4-10). The average arc of rotation of the flap was 113.5° (range 70-140°). In 3 cases, the IMAP flap was performed with a superior epigastric artery perforator flap (SEAP). In 3 cases out of 23, the flap partially necrotized, requiring surgical revision. In 1 case, the flap was fully necrotized and had to be removed. DISCUSSION AND CONCLUSION: Our series of 23 IMAP flaps on thoracic reconstruction is one of the largest published to date. Our series shows that the IMAP flap offers a simple and reliable solution with minor donor site morbidity for reconstructing small to medium-sized defects in the medial and paramedian regions of the chest wall.

What Is Hidden Behind Yellow Pixels: from Pathology to Intravascular Imaging of Atherosclerotic Plaque.

PURPOSE OF REVIEW: Intravascular imaging systems can identify lipid-rich and vulnerable plaques and help in treatment guidance. The comparability of different intracoronary imaging methods remains unclear. In this paper, we review atherosclerotic plaque pathology, plaque-stabilising effects of different lipid-lowering therapies and usage of intravascular imaging modalities. We present the results of our study in which we evaluated the correlation of the intravascular ultrasound iMAP system (iMAP-IVUS) and near-infrared spectroscopy (NIRS) in the diagnosis of vulnerable coronary plaques. RECENT FINDINGS: Lipids have an essential contribution to plaque evolution and vulnerability. Increase in plaque vulnerability alone even without increase in plaque burden defines progression of atherosclerosis. Lipidic tissue has a significant diagnostic value in patient risk stratification and can serve as a treatment target. Different vulnerable plaque parameters can be visualised with iMAP-IVUS and NIRS. Intravascular imaging systems can differ with regard to their sensitivity, specificity and limitations. Lipid-lowering therapy is crucial in plaque stabilisation.

The usefulness of the IMAP propeller flap for trachea and tracheostome reconstruction after resection of parastomal recurrence of squamous cell carcinoma following salvage total laryngectomy.

PURPOSE: Parastomal recurrence of squamous cell carcinoma (SCC) with tracheal involvement following salvage total laryngectomy after prior concurrent chemoradiotherapy is one of the most insidious challenges in head and neck surgery because a complex reconstruction is often required for covering a large area of skin loss, filling the dead space beneath, tracheal reconstruction and suspension, and tracheostome resurfacing. The aim is to describe our experience with the internal mammary artery perforator (IMAP) propeller flap for tracheal and tracheostome reconstruction and neck resurfacing after parastomal and cervical trachea resection, especially for suspension and anchoring the stump of the residual distal trachea to the island flap itself. METHODS: We describe IMAP flap reconstruction after resection of parastomal recurrence of SCC requiring cervical trachea resection in five patients between January 1, 2005 and August 30, 2019. RESULTS: IMAP propeller flap was successfully used for reconstruction after complex resection of parastomal recurrence of SCC with cervical trachea involvement in all cases. The mean length and width were, respectively, 16.8 cm (range 13-23) and 6.9 cm (range 5.5-8). We did not report complications of both the donor and the recipient site. Pharyngo-cutaneous or tracheoesophageal fistulas and wound dehiscence were not observed. CONCLUSIONS: to the best of our knowledge, this is the first report about the use of the IMAP propeller flap in this more complex clinical setting and we provide the message that this surgical procedure is worthy of consideration.

Implementation of an interprofessional medication adherence program for chronic patients in community pharmacies: how much does it cost for the provider?

BACKGROUND: The implementation of an innovative and sustainable professional pharmacy service in routine care requires substantial resources borne by the pharmacy owner. Although a community pharmacy is a business setting, few studies have examined cost as a potential barrier to widespread implementation. Implementation costs, as the cost impact of an implementation effort, can be significant and hamper the decision to invest from the provider perspective. Traditional financial planning tools can be used to analyse and support business decision to implement a service by assessing the net impact of a new service on the provider's budget. This study aimed to estimate the implementation costs and the break-even point of an interprofessional medication adherence program for chronic patients in Switzerland. The program combines motivational interviews, medication adherence electronic monitoring and feedback reports to patient and physicians. METHODS: We used a 3-step approach: (i) micro-costing analysis: identification of implementation activities, quantification and valuation of required resources. Implementation costs, including service support costs and direct delivery costs, were analysed according to the implementation phase (installation, initial implementation, and full operation); (ii) break-even analysis: estimation of the required number of patients to follow up with to ensure that the generated revenue exceeded the total cost; and (iii) univariate sensitivity analyses. RESULTS: The estimated total cost of the installation phase was 8481 CHF, more than half of which represented the cost of the equipment. Direct delivery costs were 666 CHF per patient per year, with 68% of this value associated with the cost of workforce time. According to the Swiss national reimbursement system, a minimal of 16 [10-27] patients was required to cover the implementation costs of the installation phase. This break-even point decreased to 13 patients in the initial and full operation phases. CONCLUSIONS: These estimates lead to a better understanding of the real cost of implementing a professional pharmacy service in routine care. In a Swiss context, the current medication adherence support fee-for-service system allows pharmacists to reach the break-even point. Such information is important for community pharmacists to guide their implementation strategies. The replication of similar analyses in other settings and countries is paramount.

Implementation of an interprofessional medication adherence program for HIV patients: description of the process using the framework for the implementation of services in pharmacy.

BACKGROUND: The community pharmacy center of the Department of Ambulatory Care and Community Medicine of the Policlinique Médicale Universitaire (PMU), Lausanne, Switzerland developed and implemented an interprofessional medication adherence program for chronic patients (IMAP). In 2014, a project was launched to implement the IMAP for HIV patients in a public non-academic hospital with the collaboration of community pharmacists in the Neuchâtel area (Switzerland). This article aims to describe the different implementation stages and strategies of the project. METHODS: A posteriori description of the implementation process, including the conceptualization strategies and stages (exploration, preparation, operation, sustainability) using the Framework for the Implementation of Services in Pharmacy (FISpH). RESULTS: In 2014, an attending infectious disease physician and a nurse at a public hospital (Neuchâtel, Switzerland) contacted the PMU to implement the IMAP in their setting in collaboration with community pharmacies. Five volunteer community pharmacies in Neuchâtel were trained to deliver the program. Three factors were found to be essential to the successful launch and progress of the implementation project: the experience of the community pharmacy center of the PMU with the IMAP, the involvement of the PMU research team, and collaboration with an external start up (SISPha) to train and support pharmacists. During the operation stage, the most important strategy developed was that of regular meetings between all stakeholders. These allowed healthcare professionals to discuss the implementation progress, to address each stakeholder's expectations, and to exchange experiences to facilitate interprofessional collaboration and program delivery. Structural changes allowed the formalization of the activities at the hospital and in a community pharmacy. This formalization was identified as the transition step between the operation and the sustainability stages. CONCLUSIONS: The transfer of the IMAP for HIV patients to a non-academic setting and its implementation are feasible. However, implementation of a new model of pharmacy service such as IMAP implies a deep change in practice. A transitional external support and the allocation of sufficient resources to carry out the IMAP are essential for its long-term sustainability.

Implementation study of an interprofessional medication adherence program for HIV patients in Switzerland: quantitative and qualitative implementation results.

BACKGROUND: An interprofessional medication adherence program (IMAP) for chronic patients was developed and successfully implemented in the community pharmacy of the Department of ambulatory care and community medicine (Lausanne, Switzerland). This study assesses the capacity of a physician and a nurse at the infectious diseases service of a public hospital and of community pharmacists in the Neuchâtel area (Switzerland) to implement the IMAP in their practice. METHODS: Mixed method, prospective, observational study. Quantitative and qualitative analyses of the implementation process were conducted following the RE-AIM model (reach, effectiveness, adoption, implementation and maintenance). RESULTS: Implementation started in November 2014. One physician, one nurse, and five pharmacists agreed to participate. Healthcare professionals perceived the benefits of the program and were motivated to implement it in their practice (adoption). Seventeen patients were included in the program; 13 refused to participate. The inclusion of naïve HIV patients was easier than the inclusion of experienced patients with difficult psychosocial issues (reach). Pharmacists were engaged in reinforcing patient medication adherence in 25% of interviews (effectiveness). Key facilitators expressed by healthcare professionals were patient inclusion by the physician and the nurse instead of the pharmacist and the organisation of regular meetings between all stakeholders. In contrast, the encountered barriers were the lack of time and resources, the lack of team uptake, and the lack of adoption by senior managers (implementation). Interviewed patients were all satisfied with this new program, encouraging healthcare professionals to scale it up. Structural changes allowed the hospital and one pharmacy to enter the maintenance stage (maintenance). CONCLUSION: The research team and collaboration between all professionals involved played an important role in this implementation. However, the dissemination of such a program to a larger scale and for the long term requires financial and structural resources as well as transitional external support.

iTemplate: A template-based eye movement data analysis approach.

Current eye movement data analysis methods rely on defining areas of interest (AOIs). Due to the fact that AOIs are created and modified manually, variances in their size, shape, and location are unavoidable. These variances affect not only the consistency of the AOI definitions, but also the validity of the eye movement analyses based on the AOIs. To reduce the variances in AOI creation and modification and achieve a procedure to process eye movement data with high precision and efficiency, we propose a template-based eye movement data analysis method. Using a linear transformation algorithm, this method registers the eye movement data from each individual stimulus to a template. Thus, users only need to create one set of AOIs for the template in order to analyze eye movement data, rather than creating a unique set of AOIs for all individual stimuli. This change greatly reduces the error caused by the variance from manually created AOIs and boosts the efficiency of the data analysis. Furthermore, this method can help researchers prepare eye movement data for some advanced analysis approaches, such as iMap. We have developed software (iTemplate) with a graphic user interface to make this analysis method available to researchers.

Impact of renal function on the underlying pathophysiology of coronary plaque composition in patients with type 2 diabetes mellitus.

BACKGROUND: Both the progression of diabetic kidney disease and increased glycemic variability play important roles in the pathogenesis of coronary plaque formation via inflammatory pathways in patients with type 2 diabetes mellitus (T2DM). Therefore we evaluated the role of renal function in the contributory effects of blood glucose fluctuations and blood levels of inflammatory cytokine concentrations on the tissue characteristics of coronary plaques in patients with T2DM. METHODS: We prospectively enrolled 71 T2DM patients (mean age: 68 ± 9, male 79%) with 153 coronary artery lesions. Patients were divided into 2 groups according to their estimated glomerular filtration rate (eGFR) levels: Group 1 (≥ 60 mL/min/1.73 m2, n = 40) and Group 2 (< 60 mL/min/1.73 m2, n = 31). All patients underwent continuous glucose monitoring (CGM) for 120 h and the mean amplitude of glycemic excursions (MAGE) was calculated. Serum tumor necrosis factor (TNF)-α was also measured. In addition, gray-scale coronary intravascular ultrasound (IVUS) and iMap-IVUS were performed in the coronary lesions with < 50% luminal reduction. RESULTS: In Group 1, MAGE correlated with percent lipidic volume (%LV) (r = 0.477, p = 0.002). In this group, stepwise multivariate linear regression analyses showed that only MAGE was independently associated with %LV (ß = 0.477, p = 0.002). In contrast, in Group 2, only serum TNF-α correlated with percent fibrotic volume (%FV) (r = - 0.471, p = 0.007), %LV (r = 0.496, p = 0.005) and percent necrotic volume (%NV) (r = 0.426, p = 0.017). In this group, stepwise multivariate linear regression analyses showed that only serum TNF-α was independently associated with each tissue characteristic (%FV ß = - 0.471 and p = 0.007, %LV ß = 0.496 and p = 0.005, %NV: ß = 0.426 and p = 0.017). CONCLUSIONS: In T2DM patients, the tissue characteristics of coronary plaques were associated with MAGE in patients with eGFR ≥ 60 mL/min/1.73 m2 and with serum TNF-α in those with eGFR < 60 mL/min/1.73 m2.

iMAP™ imaging of tumorous lesions surrounding the coronary arteries in a patient with an elevated serum level of immunoglobulin G4.

A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAP™, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252-427 mg/dL (8 measurements) (reference range, 4.8-105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4.

Facial Pain Triggered by Inferior Turbinate Partial Resection in a Patient with a Previous History of Inferior Meatal Antrostomy: A Case Report.

OBJECTIVES: Inferior meatal antrostomy (IMA) is regarded as a safe method, with minimal complications, for managing various lesions in the maxillary sinus. However, in patients with persisting IMA window, resection of the inferior turbinate may result in direct airflow into the antrum, irritating the antral mucosa. METHODS: Case report and review of literature. RESULTS/CASE: The present report describes a 29-year-old man who previously underwent unilateral IMA for the excision of a dentigerous cyst. The patient did not report any facial pain following the excision of the cyst. One year later, this patient underwent partial resection of the inferior turbinate for the resolution of nasal stuffiness by another surgeon. Soon after surgery, the patient developed severe facial and ocular pain on the side of the IMA, with the pain being especially aggravated upon inhalation. Endoscopy and computed tomography (CT) revealed a persisting IMA window. The patient's severe discomfort was thought to result from direct airflow into the maxillary sinus, as the resected turbinate may have altered normal nasal airflow. A unilateral inferior meatal augmentation procedure (IMAP) with an autologous ear cartilage implant was performed, resulting in complete relief of pain and discomfort. CONCLUSIONS: Although IMA alone is a relatively safe surgical procedure, care should be taken when performing inferior turbinoplasty in patients with persistent IMA opening.

Outcomes of internal mammary artery perforator flap in head and neck reconstruction: A systematic review.

This study aims to evaluate the functional and prognostic outcomes associated with the internal mammary artery perforator (IMAP) flap in various head and neck defect repairs, given the current lack of clarity on its effectiveness. We performed a systematic review of various databases: PubMed, Embase, Scopus, Web of Science, and ScienceDirect using keywords such as "Internal mammary artery perforator flap" and "IMAP." Screening and data extractions were performed by two individual reviewers. Articles were considered eligible if they included sufficient information on IMAP flap features, their applications in the head and neck, and outcomes. From 264 articles analyzed, 24 studies were included for qualitative analysis. Out of which, 125 patients who received internal mammary artery perforator flaps were included. Most of the patients, 103 (88%), received pedicled IMAP flaps, and 22 (12%) received IMAP free flaps. The second internal mammary artery (IMA) was favored as the single perforator (81.5%), with the combination of the first and second IMA being the primary choice for dual perforators (92.5%). IMAP flaps were predominantly single perforator flaps (65%), with 35% being dual perforator flaps. Among various applications, IMAP flaps are commonly employed in the reconstruction of neck defects (25.5%), pharyngocutaneous fistula repair (20.8%), and burn scar contracture restoration (8%). Only seven (5.6%) patients had flap complications, including venous congestion (1.6%), partial necrosis (1.6%), complete necrosis (1.6%), and incision dehiscence (0.8%). Donor sites were predominantly closed by the primary closure (92%). 3.2% of donor sites had minor complications. The average follow-up was 12.6 (IQR: 6-18) months. This systematic review highlights the effectiveness and safety of IMAP flaps in head and neck reconstruction, with positive outcomes and minimal complications.

Kamolonol suppresses angiotensin II-induced stress fiber formation and cellular hypertrophy through inhibition of Rho-associated kinase 2 activity.

Kamolonol (7-[[(1R,2R,4R,4aS,5R,8aS)-4-hydroxy-1,2,4a,5-tetramethyl-6-oxo-3,4,5,7,8,8a-hexahydro-2H-naphthalen-1-yl]methoxy]chromen-2-one) is a sesquiterpene coumarin and an active component of gum extracts from Ferulaassafoetida. The aim of this study was to investigate the anti-fibrotic and anti-cellular hypertrophic effects of kamolonol, and further to explore its possible mechanism. Kamolonol (3-30µM) significantly inhibited stress fiber formation induced by angiotensin II (Ang II) in rat heart-derived H9c2 cells. Furthermore, kamolonol (3-30µM) showed a potent inhibitory effect on Ang II-induced cellular hypertrophy in H9c2 cells. Next, a Rho-associated kinase (ROCK) activity was measured because actin stress fiber formation and/or cellular hypertrophy are usually induced by the activation of ROCK. Rho-associated kinase 2 (ROCK2) studies using a time-resolved fluorescence resonance energy transfer (TR-FRET) showed that kamolonol possesses a potent ROCK2 inhibitory activity with IC50 values of 2.27µM, and has an ATP-competitive inhibitory mode. In validation study, pretreatment of kamolonol (3-30µM) for 2h decreased the Ang II-induced phosphorylation of myosin phosphatase 1 (MYPT1) and myosin light chain 2 (MLC2). Taken together, these results indicate that kamolonol suppresses Ang II-induced stress fiber formation and cellular hypertrophy, and propose that one mechanism underlying these anti-fibrotic and anti-cellular hypertrophic effects involves inhibition of the ROCK-MLC pathway.

The shark flap: a modified internal mammary artery perforator flap for composite defects in head and neck reconstruction.

This report describes a multi-vector variant of IMAP flap which allows to reconstruct composite head and neck defects. It was named the 'shark flap' because of its shape: a main body (the regular IMAP) and a superior 'fin' based on a randomic vascular pathway.

Setting thresholds is not enough: Beach litter as indicator of poor environmental status in the southern Adriatic Sea.

This study deals with the issue of beach litter pollution in the context of the Descriptor 10 of the Marine Strategy Framework Directive Good Environmental Status of EU waters and Ecological objective 10, Common indicator 22 of IMAP. Analyses of the amount, distribution and categorization of beach litter were conducted on nine beaches during 108 surveys covering the area of 206.620 m2 in Albania, Italy and Montenegro. Our findings showed that the level of beach litter pollution on south Adriatic beaches is significantly above the adopted threshold values, with a median item numbers of 327, 258 and 234 per 100 m of beach stretch for Albania, Italy and Montenegro, respectively. It can be concluded that, when it comes to beach litter pollution, GES has not been achieved. Given the defined baseline and threshold values at the EU level, the process of reducing the total amount of marine litter in southern Adriatic Sea will be very challenging and needs urgent and specific actions.

Identification of the GTPase IMAP family as an immune-related prognostic biomarker in the breast cancer tumor microenvironment.

INTRODUCTION: Breast cancer is the most common malignancy threatening women's health worldwide. The GTPase IMAP family genes are proteins belonging to the immune-associated nucleotide subfamily of the GTP-binding superfamily and nucleotide-binding proteins. However, little is known about the role of different GTPase IMAP family genes in breast cancer. METHODS: We obtained differential genes from the GEPIA and UALCAN databases and then used the Kaplan-Meier plotter, The Human Protein Atlas, NetworkAnalyst, STRING, and TIMER to analyze the prognostic value, protein expression, and immune cell infiltration of the GTPase IMAP family in patients with breast cancer. RESULTS: Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly low in breast tumor tissues. In the overall population, patients with high expression of all genes of the GIMAP family had a significantly higher overall survival (OS), with the most significant increase correlated with the GIMAP2 gene (hazard ratio [HR] = 0.45, 95% confidence interval [CI], 0.34-0.59, P = 3.1e-09). However, patients with high expression of the GIMAP family genes in triple-negative breast cancer compared to those with low expression had a significant OS benefit, with the most pronounced benefit correlated with the GIMAP2 gene (HR = 0.37, 95% CI, 0.23-0.59, P = 1.4e-05). GIMAP7 and GIMAP8 were significantly upregulated in breast tumor tissues. The expression of genes in different GIMAP families was positively correlated with the infiltration and expression of six immune cell types (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells). CONCLUSION: This study may provide novel insights into the selection of GIMAP family prognostic biomarkers for breast cancer.

Case Report: Revisiting the Internal Mammary Artery Perforator Flap: Salvage Option for Circumferential Pharyngo-Esophageal Defects.

Patients that present with pharyngeal strictures and pharyngocutaneous fistulas in the context of previous reconstruction and post-operative radiotherapy often report significant morbidity and reduction in quality of life. Reconstruction of such defects present a substantial clinical challenge requiring the importation of unirradiated vascularized tissue to facilitate healing in a friable, fibrotic, and vessel depleted tissue bed. The authors present a case report demonstrating an adaptation of the internal mammary artery perforator (IMAP) flap for reliable reconstruction of circumferential pharyngeal defects with primary tension free closure of the donor site. This technique avoids the use of free tissue transfer in a hostile, irradiated neck. The tubed IMAP flap is an excellent option, serving the purposes of reconstruction as well as addressing the patient's presenting issues of a chronic sinus and pharyngeal stricture inhibiting oral intake.

Inferior meatus augmentation procedure (IMAP) normalizes nasal airflow patterns in empty nose syndrome patients via computational fluid dynamics (CFD) modeling.

BACKGROUND: Empty nose syndrome (ENS) is a controversial upper airway disorder most commonly associated with tissue loss from the inferior turbinates. The inferior meatus augmentation procedure (IMAP) has been shown to effectively reduce ENS symptoms in a durable manner, but the precise mechanisms that may govern this symptomatic improvement remain unknown. METHODS: Five patients with ENS who underwent bilateral IMAP via submucosal costal cartilage implant were assessed. Pre-implant and 6 months post-implant computed tomography (CT) imaging for each ENS patient was analyzed in a blinded fashion using computational fluid dynamics (CFD) modeling to investigate intrapatient changes in airflow parameters. RESULTS: Following surgery, ENS patients have significantly improved symptoms as indexed by Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) scoring (pre-implant: 14.00 ± 4.06 [mean ± standard deviation]; 95% confidence interval [CI], 10.44 to 17.56; post-implant: 4.8 ± 2.77; 95% CI, 2.37 to 7.23; Cohen's d = 2.64; p = 0.02). Using CFD, a significant shift in nasal airflow patterns was observed, where airflow deviates away from the middle meatus upon hitting the implant (pre-implant: 67.13% ± 11.14%; 95% CI, 60.22% to 74.04%; post-implant: 46.18% ± 12.81%; 95% CI, 38.23% to 54.12%; d = 1.74; p < 0.05) toward the inferior meatus (pre-implant: 30.55% ± 11.29%; 95% CI, 23.55% to 37.55%; post-implant: 42.59% ± 9.60%; 95% CI, 36.63 to 48.54%; d = 1.14; p < 0.05). No significant changes were found in nasal resistance (pre-implant: 0.102 ± 0.015; 95% CI, 0.092 to 0.112 Pa*s/mL; post-implant: 0.105 ± 0.041; 95% CI, 0.081 to 0.130 Pa*s/mL). In addition, the improvement of ENS6Q scoring significantly correlated with percent reduction in aberrant airflow through the middle meatus (R2 = 0.60, p = 0.04). CONCLUSION: This study supports our prior working hypothesis that disordered vectors of nasal airflow congregate in the middle meatus contribute to ENS symptoms, not nasal resistance. Moreover, these data illuminate a paradoxical, but consistent, restoration of nasal airflow to the inferior meatus following the replacement of turbinate tissue volume in the inferior meatus via IMAP surgery, potentially due to the Coanda effect.

Effect of evolocumab on the progression and stability of atherosclerotic plaques as evaluated by grayscale and iMAP-IVUS.

BACKGROUND: Evolocumab inhibits the proprotein convertase subtilisin/kexin type 9 protein and is a potent cholesterol-lowering drug. However, the relationship between evolocumab and inflammation, and the effects of evolocumab on the stability of atherosclerotic plaques remain unknown. METHODS: Twenty-seven purebred New Zealand rabbits were fed with an atherogenic diet for 2 weeks. The abdominal aortic endothelium was balloon-injured. The rabbits were divided into the atorvastatin (2 mg/kg/day; Ato), evolocumab (7 mg/kg/2 weeks, Evo) and control groups. Intravascular ultrasound (IVUS) images of the abdominal artery were analyzed at 10 and 18 weeks. Additionally, the serum levels of the biomarkers were measured at baseline, and at 10 and 18 weeks. RESULTS: The serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and monocyte chemoattractant protein-1 (MCP-1) increased after 10 weeks of administration of the proatherosclerotic diet, while the levels of high-density lipoprotein cholesterol (HDL-C) and transforming growth factor-ß (TGF-ß) decreased. The reduction in the serum levels of triglycerides, total cholesterol, LDL-C, MCP-1, TGF-ß, and toll-like receptor 4 (TLR4) following treatment with evolocumab was higher than that of atorvastatin. Both evolocumab and atorvastatin reduced the percent atheroma volume. Evolocumab increased the fibrotic% and decreased the necrotic%. Correlation analysis revealed that the levels of triglycerides, total cholesterol, LDL-C, MCP-1, TGF-ß, and TLR4 were negatively correlated with the fibrotic%, but were positively correlated with the necrotic%. Multivariate linear regression analysis revealed that treatment with atorvastatin, and especially evolocumab, was a consistent predictor of the percent atheroma volume, and fibrotic and necrotic composition. CONCLUSIONS: Proprotein convertase subtilisin/kexin type 9 regulates the serum levels of lipid and cholesterol may via inflammatory pathways. The results also indicate that evolocumab is more potent than atorvastatin in suppressing the progression and stability of atherosclerotic plaque in rabbits.

Coronary plaque tissue characterization in patients with premature coronary artery disease.

Premature coronary artery disease (CAD) studies rarely involve coronary plaque characterization. We characterize coronary plaque tissue by radiofrequency intravascular ultrasound (IVUS) in patients with premature CAD. From July 2015 to December 2017, 220 patients from the Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine with first occurrence of angina or myocardial infarction within 3 months were enrolled. Patients with premature CAD (n = 47, males aged < 55 years, and females aged < 65 years) or later CAD (n = 155) were retrospectively compared for cardiovascular risk factors, laboratory examination findings, coronary angiography data, gray-scale IVUS, and iMap-IVUS. The mean age was 53.53 ± 7.24 vs. 70.48 ± 8.74 years (p < 0.001). The groups were similar for traditional coronary risk factors except homocysteine (18.60 ± 5.15 vs. 17.08 ± 4.27 µmol/L, p = 0.043). After matching for baseline characteristics, LDL cholesterol (LDL-C) was higher for premature CAD than later CAD (2.50 ± 0.96 vs. 2.17 ± 0.80 mmol/L, p = 0.019). Before the matching procedure, the premature CAD group had shorter target lesion length [18.50 (12.60-32.00) vs. 27.90 (18.70-37.40) mm, p = 0.002], less plaque volume [175.59 (96.60-240.50) vs. 214.73 (139.74-330.00) mm3, p = 0.013] than the later CAD group. After the matching procedure, the premature CAD group appeared to be less plaque burden (72.69 ± 9.99 vs. 74.85 ± 9.80%, p = 0.005), and positive remodeling (1.03 ± 0.12 vs. 0.94 ± 0.18, p = 0.034), and lower high risk feature incidence (p = 0.006) than the later CAD group. At the plaque's minimum lumen, premature CAD had more fibrotic (p < 0.001), less necrotic (p = 0.001) and less calcified areas (p = 0.012). Coronary plaque tissue was more fibrotic with less necrotic and calcified components in premature than in later CAD, and the range and degree of atherosclerosis were significantly lower.