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1.
J Inflamm Res ; 17: 865-880, 2024.
Article in English | MEDLINE | ID: mdl-38348276

ABSTRACT

Purpose: The purpose of this study was to analyze the nasal lymphatic system in order to uncover novel factors that might be involved in pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP). Patients and Methods: Lymphatic vessels (LVs) and macrophages were localized and counted in the inferior and middle turbinate, the uncinate process and the ethmoid of CRSwNP and CRSsNP patients, the NP and the inferior turbinate of controls (n≥6 per group). Lysates of the same tissue types (n=7 per group) were analyzed for lymphatic vessel endothelial receptor 1 (LYVE-1), for matrix metalloproteinase 14 (MMP-14) and for Hyaluronic acid (HA) using ELISA. HA was localized in sections of CRSwNP NP, CRSsNP ethmoid and control inferior turbinate (n=6 per group). The results of HA levels were correlated to the number of macrophages in tissues. The nasal secretions of CRSwNP (n=28), CRSsNP (n=30), and control (n=30) patients were analyzed for LYVE-1 and HA using ELISA. Results: The number of LVs was significantly lower in tissues of both CRS groups compared to the control. In the tissue lysates, LYVE-1 expression differed significantly between the CRSwNP tissues with a particularly high level in the NP. MMP-14 was significantly overexpressed in CRSwNP uncinate process. There were no significant differences in tissue HA expression. In the mucus LYVE-1 was significantly underexpressed in CRSsNP compared to CRSwNP and control, while HA was significantly underexpressed in both CRS groups. In the NP, HA and macrophages were accumulated particularly below the epithelium. Tissue levels of HA revealed a significant positive correlation with the number of macrophages. Conclusion: CRS might be associated with an insufficient clearing of the nasal mucosa through the lymphatics. The accumulation of HA and macrophages might promote inflammation, fluid retention, and polyp formation. These results may provide novel CRS-associated factors.

2.
Article in English | MEDLINE | ID: mdl-37990964

ABSTRACT

OBJECTIVE: The objective of this study was to analyze advantages and disadvantages of mucus and serum for biomarker analysis. METHODS: This study includes prospective study of 61 CRS with nasal polyps patients who were followed over 24 months and over nine time points after functional endoscopic sinus surgery. At each time points, the nasal polyp score (NPS) was assessed and mucus as well as serum was collected. Selected were measured in mucus and serum. Mean, standard deviation and variance, undetectable values, and the correlation of the biomarkers to the NPS over time and to early recurrences were calculated, and the effect of surgery on the biomarkers was assessed. Additionally, the diurnal rhythm of all biomarkers was measures in order to assure stable biomarker values during sampling times. RESULTS: All biomarkers showed stable values during sampling times. Serum biomarker levels displayed higher percentages of undetectable values compared to mucus biomarkers. Mucus periostin (p < 0.001, r = 0.89), mucus IgE (p < 0.001, r = 0.51), serum periostin (p < 0.001, r = 0.53), mucus CST1 (p < 0.001, r = 0.27), and serum IgE (p < 0.01, r = -0.18) were the best marker and medium combinations to track the NPS over time and to predict recurrences. Mucus serpinF2 was negatively correlated and predicted early recurrences (p = 0.026, R2  = 0.015). CONCLUSIONS: Serum and mucus both represent viable mediums for "liquid biopsies." The most promising biomarker/medium combinations over time to track disease severity were mucus periostin, mucus IgE, serum periostin, mucus CST1, and serum IgE. Mucus serpinF2 was the best biomarker to predict early recurrences.

4.
Bioengineering (Basel) ; 10(10)2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37892860

ABSTRACT

Synthetic silicone larynx models are essential for understanding the biomechanics of physiological and pathological vocal fold vibrations. The aim of this study is to investigate the effects of artificial ligament fibers on vocal fold vibrations in a synthetic larynx model, which is capable of replicating physiological laryngeal functions such as elongation, abduction, and adduction. A multi-layer silicone model with different mechanical properties for the musculus vocalis and the lamina propria consisting of ligament and mucosa was used. Ligament fibers of various diameters and break resistances were cast into the vocal folds and tested at different tension levels. An electromechanical setup was developed to mimic laryngeal physiology. The measurements included high-speed video recordings of vocal fold vibrations, subglottal pressure and acoustic. For the evaluation of the vibration characteristics, all measured values were evaluated and compared with parameters from ex and in vivo studies. The fundamental frequency of the synthetic larynx model was found to be approximately 200-520 Hz depending on integrated fiber types and tension levels. This range of the fundamental frequency corresponds to the reproduction of a female normal and singing voice range. The investigated voice parameters from vocal fold vibration, acoustics, and subglottal pressure were within normal value ranges from ex and in vivo studies. The integration of ligament fibers leads to an increase in the fundamental frequency with increasing airflow, while the tensioning of the ligament fibers remains constant. In addition, a tension increase in the fibers also generates a rise in the fundamental frequency delivering the physiological expectation of the dynamic behavior of vocal folds.

5.
JACC Cardiovasc Interv ; 16(17): 2112-2119, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37704297

ABSTRACT

BACKGROUND: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). OBJECTIVES: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). METHODS: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. RESULTS: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. CONCLUSIONS: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate.


Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Vascular Diseases , Humans , Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome
6.
Nucl Med Commun ; 44(11): 968-976, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37661777

ABSTRACT

INTRODUCTION: A significant proportion of patients with carcinoid syndrome develop carcinoid heart disease (CHD). Valve degeneration can lead to right heart failure, and worsening prognosis. Replacement of affected valves is an effective therapy. We reviewed patients treated with valve replacement to assess prognostic factors. METHODS: CHD patients records who underwent valve replacement from 2003-2019 were reviewed. RESULTS: Twenty-six patients underwent valve replacement. Mean (SD) age was 61 (11) years, 54% female. Eleven tumours were grade G1, with the remaining G2. NYHA pre-surgery mean (SD) 2.0 (0.7); post-surgery mean 1.2; follow-up mean (SD) 1.6 (0.8). Mean NYHA score difference from pre- to post-surgery -0.71 ( P  = 0.002). 88.5% two (PR & TR), 3.9% one, 3.9% three and 3.9% four valves replaced. 13 patients received Lu177 oxodotreotide; 27% completed four cycles. Mortality at 1 and 5 years follow up was 42% and 50% respectively. Cox proportional hazards model of survival from surgery, adjusting for age [hazard ratio (HR) 0.96 (0.89-1.03) ( P  = 0.25)], four cycles of Lu177 oxodotreotide demonstrated HR 0.087 (0.0079-0.95) ( P  = 0.045) indicating improved survival. DISCUSSION: Surgical patients were often NYHA grade II, and symptoms improved post-surgery. Four cycles of Lu177 oxodotreotide improved survival, although the confidence interval was wide. Further studies should be performed to assess Lu177 oxodotreotide in CHD.


Subject(s)
Carcinoid Heart Disease , Heart Valve Diseases , Heart Valve Prosthesis Implantation , Humans , Female , Middle Aged , Male , Heart Valve Diseases/surgery , Heart Valve Diseases/diagnosis , Treatment Outcome , Heart Valve Prosthesis Implantation/adverse effects , Carcinoid Heart Disease/diagnostic imaging , Carcinoid Heart Disease/surgery , Prognosis
7.
Expert Rev Pharmacoecon Outcomes Res ; 23(9): 1087-1099, 2023.
Article in English | MEDLINE | ID: mdl-37638585

ABSTRACT

OBJECTIVE: Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective. METHODS: A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted to explore the uncertainty around the parameters. RESULTS: The novel tissue valve was potentially associated with higher quality-adjusted life years (QALYs) of 0.01 per person. Potential cost savings were greatest for those aged 55-64 (£408) versus those aged 65+(£53). DSA indicated the results to be most dependent on relative differences in general mortality, procedure costs, and reoperation rates. PSA estimated around 75% of the iterations to be cost-effective at £20,000 per QALY for those aged 55-64, and 57% for those aged 65+. CONCLUSIONS: The exploratory analysis suggests that the novel tissue valve could be a cost-effective intervention for people over the age of 55 with AS who are suitable for SAVR in the UK.


Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Male , Humans , Aortic Valve/surgery , Heart Valve Prosthesis Implantation/methods , Cost-Effectiveness Analysis , State Medicine , Prostate-Specific Antigen , Treatment Outcome , Cost-Benefit Analysis , Aortic Valve Stenosis/surgery , United Kingdom
8.
Circulation ; 148(12): 950-958, 2023 09 19.
Article in English | MEDLINE | ID: mdl-37602376

ABSTRACT

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.


Subject(s)
Coronary Artery Disease , Fractional Flow Reserve, Myocardial , Myocardial Infarction , Percutaneous Coronary Intervention , Stroke , Humans , Coronary Artery Disease/surgery , Follow-Up Studies , Percutaneous Coronary Intervention/adverse effects , Coronary Artery Bypass/adverse effects , Stroke/epidemiology , Stroke/etiology
9.
J Voice ; 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37648625

ABSTRACT

OBJECTIVE: The first goal of this study was to investigate the coverage of laryngeal structures using two potential administration techniques for synthetic mucus: inhalation and lozenge ingestion. As a second research question, the study investigated the potential effects of these techniques on standardized voice assessment parameters. METHODS: Fluorescein was added to throat lozenges and to an inhalation solution to visualize the coverage of laryngeal structures through blue light imaging. The study included 70 vocally healthy subjects. Fifty subjects underwent administration via lozenge ingestion and 20 subjects performed the inhalation process. For the first research question, the recordings from the blue light imaging system were categorized to compare the extent of coverage on individual laryngeal structures objectively. Secondly, a standardized voice evaluation protocol was performed before and after each administration to determine any measurable effects of typical voice parameters. RESULTS: The administration via inhalation demonstrated complete coverage of all laryngeal structures, including the vocal folds, ventricular folds, and arytenoid cartilages, as visualized by the fluorescent dye. In contrast, the application of the lozenge predominantly covered the pharynx and laryngeal surface toward the aryepiglottic fold, but not the inferior structures. All in all, the comparison before and after administration showed no clear effect, although a minor deterioration of the acoustic signal was noted in the shimmer and cepstral peak prominence after the inhalation. CONCLUSIONS: Our findings indicate that the inhalation process is a more effective technique for covering deeper laryngeal structures such as the vocal folds and ventricular folds with synthetic mucus. This knowledge enables further in vivo studies on the role of laryngeal mucus in phonation in general, and how it can be substituted or supplemented for patients with reduced glandular activity as well as for heavy voice users.

10.
Article in English | MEDLINE | ID: mdl-37462612

ABSTRACT

OBJECTIVES: We report 1-year safety and clinical outcomes in patients <60 years undergoing bioprosthetic surgical aortic valve intervention. METHODS: The INSPIRIS RESILIA Durability Registry is a prospective, multicentre registry to assess clinical outcomes of patients <60 years. Patients with planned SAVR with or without concomitant replacement of the ascending aorta and/or coronary bypass surgery were included. Time-related valve safety, haemodynamic performance and quality of life (QoL) at 1 year were assessed. RESULTS: A total of 421 patients were documented with a mean age of 53.5 years, 76.5% being male and 27.2% in NYHA class III/IV. Outcomes within 30 days included cardiovascular-related mortality (0.7%), time-related valve safety (VARC-2; 5.8%), thromboembolic events (1.7%), valve-related life-threatening bleeding (VARC-2; 4.3%) and permanent pacemaker implantation (3.8%). QoL was significantly increased at 6 months and sustained at 1 year. Freedom from all-cause mortality at 1 year was 98.3% (95% confidence interval 97.1; 99.6) and 81.8% were NYHA I versus 21.9% at baseline. No patient developed structural valve deterioration stage 3 (VARC-3). The mean aortic pressure gradient was 12.6 mmHg at 1 year and the effective orifice area was 1.9 cm2. CONCLUSIONS: The 1-year data from the INSPIRIS RESILIA valve demonstrate good safety and excellent haemodynamic performance as well as an early QoL improvement. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03666741.

11.
Front Immunol ; 14: 1075066, 2023.
Article in English | MEDLINE | ID: mdl-36969262

ABSTRACT

Introduction: The objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures. Methods: This was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels. Results: 106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups. Conclusion: In conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.


Subject(s)
Nasal Polyps , Rhinitis , Sinusitis , Humans , Nasal Polyps/complications , Nasal Polyps/drug therapy , Nasal Polyps/surgery , Prednisolone/therapeutic use , Quality of Life , Prospective Studies , Rhinitis/complications , Rhinitis/drug therapy , Rhinitis/surgery , Sinusitis/drug therapy , Sinusitis/surgery , Sinusitis/complications , Steroids
12.
J Voice ; 2023 Mar 25.
Article in English | MEDLINE | ID: mdl-36973131

ABSTRACT

OBJECTIVE: Patients suffering from ectodermal dysplasia (ED), which is an inherited disorder in the development of the ectodermal structures, have a significantly reduced expression of teeth, hair, sweat glands, and salivary glands in the respiratory tract including the larynx. Previous studies within the framework of the present project showed a significantly reduced saliva production and an impairment of the acoustic outcome in ED patients compared to the control group. However, until now, no statistically significant difference between EDs and controls could be found regarding vocal fold dynamics in the high-speed videoendoscopy (HSV) recordings using representative parameters on closure, symmetry, and periodicity. The aim of this study is to examine the role of tissue characteristics by means of objective mechanical parameters derived from HSV recordings. METHODS: This study includes 28 ED patients and 42 controls (no ED, healthy voice). The vocal fold oscillations were recorded by high-speed videoendoscopy (HSV@4kHz). Based on the dynamical measures of the glottal area waveform (GAW), objective glottal dynamic parameters associated with tissue properties like flexibility and stiffness were computed. RESULTS: The present evaluation displays a significant difference between male ED patients and male controls concerning the HSV-based mechanical parameters indicating reduced stiffness and increased deformability for the vocal folds of male ED patients. In contrast to strongly amplitude-dependent parameters, the primarily velocity-based parameters showed no statistically significant deviation. CONCLUSIONS: The presented data provides the first promising indication toward the underlying causes on the laryngeal level leading to the voice conspicuities in ED patients. The significant difference concerning the mechanical parameters suggests a different composition of the extracellular matrix of the tissue of the vocal folds of ED patients compared to controls.

13.
Heart ; 109(17): e2, 2023 08 11.
Article in English | MEDLINE | ID: mdl-36898706

ABSTRACT

Infective endocarditis (IE) remains a difficult condition to diagnose and treat and is an infection of high consequence for patients, causing long hospital stays, life-changing complications and high mortality. A new multidisciplinary, multiprofessional, British Society for Antimicrobial Chemotherapy (BSAC)-ledWorking Party was convened to undertake a focused systematical review of the literature and to update the previous BSAC guidelines relating delivery of services for patients with IE. A scoping exercise identified new questions concerning optimal delivery of care, and the systematic review identified 16 231 papers of which 20 met the inclusion criteria. Recommendations relating to endocarditis teams, infrastructure and support, endocarditis referral processes, patient follow-up and patient information, and governance are made as well as research recommendations. This is a report of a joint Working Party of the BSAC, British Cardiovascular Society, British Heart Valve Society, British Society of Echocardiography, Society of Cardiothoracic Surgeons of Great Britain and Ireland, British Congenital Cardiac Association and British Infection Association.


Subject(s)
Endocarditis, Bacterial , Endocarditis , Humans , Consensus , Endocarditis, Bacterial/diagnosis , Endocarditis/therapy , Endocarditis/drug therapy , United Kingdom , Ireland
14.
J Voice ; 37(6): 913-923, 2023 Nov.
Article in English | MEDLINE | ID: mdl-34353685

ABSTRACT

OBJECTIVE: Patients with ectodermal dysplasia (ED) suffer from an inherited disorder in the development of the ectodermal structures. Besides the main symptoms, i.e. significantly reduced formation/expression of teeth, hair and sweat glands, a decreased saliva production is objectively accounted. In addition to difficulties with chewing/swallowing, ED patients frequently report on the subjective impression of rough and hoarse voices. A correlation between the reduced production of saliva and an affliction of the voice has not yet been investigated objectively for this rare disease. METHODS: Following an established measurement protocol, a study has been conducted on 31 patients with ED and 47 controls (no ED, healthy voice). Additionally, the vocal fold oscillations were recorded by high-speed videoendoscopy (HSV@4 kHz). The glottal area waveform was determined by segmentation and objective glottal dynamic parameters were calculated. The generated acoustic signal was evaluated by objective and subjective measures. The individual impairment was documented by a standardized questionnaire (VHI). Additionally, the amount of generated saliva was measured for a defined period of time. RESULTS: ED patients displayed a significantly reduced saliva production compared to the control group. Furthermore, the auditory-perceptual evaluation yielded significantly higher ratings for breathiness and hoarseness in the voices of male ED patients compared to male controls. The majority of male ED patients (67%) indicated at least minor impairment in the self-evaluation. Objective acoustic measures like Jitter and Shimmer confirmed the decreased acoustic quality in male ED patients, whereas none of the investigated HSV parameters showed significant differences between the test groups. Statistical analysis did not confirm a statistically significant correlation between reduced voice quality and amount of saliva. CONCLUSIONS: An objective impairment of the acoustic outcome was demonstrated for male ED patients. However, the vocal folds dynamics in HSV recordings seem unaffected.


Subject(s)
Ectodermal Dysplasia , Saliva , Humans , Male , Phonation , Vocal Cords , Voice Quality , Hoarseness
15.
Am J Rhinol Allergy ; 37(3): 348-359, 2023 May.
Article in English | MEDLINE | ID: mdl-36341722

ABSTRACT

BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) represents a phenotype of CRS, whose immunological mechanisms are still unclear. So far there are neither suitable biomarkers to determine the course of the disease nor an individual therapy. OBJECTIVE: The purpose of this study was to characterize the CRSsNP endotype by identifying and validating non-invasive proteomic biomarkers. METHODS: A highly-multiplexed proteomic array consisting of antibodies against 2000 proteins was used to identify proteins that are differentially expressed in the nasal mucus of the CRSsNP and control groups (n = 7 per group). The proteins identified to be most differentially expressed were validated in matched nasal mucus samples using western blots and enzyme-linked immunosorbent assay (ELISA). Validation was also done in a second cohort using western blots (CRSsNP n = 25, control n = 23) and ELISA (n = 30 per group). Additionally, immunohistochemistry in CRSsNP and control tissue samples was performed to characterize the selected proteins further. RESULTS: Out of the 2000 proteins examined, 7 from the most differentially expressed proteins were chosen to be validated. The validation results showed that 4 proteins were significantly upregulated in CRSsNP mucus, including macrophage inflammatory protein-1beta (MIP-1ß), resistin, high mobility group box 1 (HMGB1), and forkhead box protein 3 (FOXP3). Cartilage acidic protein 1 (CRTAC1) was not significantly upregulated. Two proteins were significantly downregulated including scavenger receptor class F member 2 (SCARF2) and P-selectin. All proteins selected are mainly associated with inflammation, cell proliferation/differentiation, apoptosis and cell-cell or cell-matrix interaction. CONCLUSION: Proteomic analysis of CRSsNP and control mucus has confirmed known and revealed novel disease-associated proteins that could potentially serve as a new biosignature for CRSsNP. Analysis of the associated pathways will specify endotypes of CRSsNP and will lead to an improved understanding of the pathophysiology of CRSsNP. Furthermore, our data contribute to the development of a reproducible, non-invasive, and quantitative "liquid biopsy" for rhinosinusitis.


Subject(s)
Nasal Polyps , Rhinitis , Sinusitis , Humans , Proteome/metabolism , Proteomics , Mucus/metabolism , Biomarkers , Chronic Disease , Calcium-Binding Proteins
16.
J Acoust Soc Am ; 152(6): 3245, 2022 12.
Article in English | MEDLINE | ID: mdl-36586828

ABSTRACT

Laryngeal mucus hydrates and lubricates the deformable tissue of the vocal folds and acts as a boundary layer with the airflow from the lungs. However, the effects of the mucus' viscoelasticity on phonation remain widely unknown and mucus has not yet been established in experimental procedures of voice research. In this study, four synthetic mucus samples were created on the basis of xanthan with focus on physiological frequency-dependent viscoelastic properties, which cover viscosities and elasticities over 2 orders of magnitude. An established ex vivo experimental setup was expanded by a reproducible and controllable application method of synthetic mucus. The application method and the suitability of the synthetic mucus samples were successfully verified by fluorescence evidence on the vocal folds even after oscillation experiments. Subsequently, the impact of mucus viscoelasticity on the oscillatory dynamics of the vocal folds, the subglottal pressure, and acoustic signal was investigated with 24 porcine larynges (2304 datasets). Despite the large differences of viscoelasticity, the phonatory characteristics remained stable with only minor statistically significant differences. Overall, this study increased the level of realism in the experimental setup for replication of the phonatory process enabling further research on pathological mucus and exploration of therapeutic options.


Subject(s)
Larynx , Swine , Animals , Larynx/physiology , Vocal Cords/physiology , Phonation/physiology , Mucus , Acoustics
17.
J Card Surg ; 37(12): 4598-4605, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36284463

ABSTRACT

INTRODUCTION: In mitral valve replacement (MVR), sudden increases in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes left ventricular (LV) dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favorable outcome on LV function. However, there is paucity of data on the impact of complete preservation of the sub-valvular apparatus (MVR-C). OBJECTIVE: We investigated the impact of MVR-P and MVR-C on baseline and 3-months postoperative LV ejection fraction (EF) and global longitudinal strain (GLS). METHODS: We retrospectively analyzed a cohort of 29 MVR-P and 19 MVR-C patients with complete echocardiography data at our unit, who were operated between 2008 and 2017. Between-group changes in LVEF and GLS were compared using independent sample T-test. RESULTS: Median age was 59 years (IQR 50-69 years). Baseline LVEF was 58% (51%- 60%). Baseline GLS was -18.4 (-21.2 to -15.5). There were no significant between-group differences between all baseline demographics and echocardiographic markers. There was significantly higher absolute postoperative LVEF in MVR-C patients (p = 0.029). There was also significant worsening in LVEF (p = 0.0121) and GLS (p < 0.0001) after MVR-P and not MVR-C, suggesting no reduction in LV function post-MVR-C but a reduction post-MVR-P. There was significantly less postoperative worsening of GLS per patient in MVR-C group as compared to the MVR-P group (p = 0.023), indicating better preservation of LV function. There was also a smaller decline in LVEF per patient in the MVR-C as compared to the MVR-P group, although not statistically significant (p = 0.23). CONCLUSION: MVR with complete preservation of the sub-valvular apparatus shows a favorable impact on the longitudinal function of the heart at 3 months. Further studies with larger patient numbers are indicated to investigate the long-term results of this surgical approach.


Subject(s)
Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Ventricular Dysfunction, Left , Humans , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Ventricular Function, Left , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/surgery , Mitral Valve Insufficiency/complications , Retrospective Studies , Stroke Volume , Ventricular Dysfunction, Left/etiology , Heart Valve Prosthesis Implantation/methods
18.
J Card Surg ; 37(12): 4278-4284, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36208103

ABSTRACT

OBJECTIVES: The results of coronary artery bypass graft (CABG) surgery with total arterial revascularisation (TA-CABG) in elderly patients, who may have insufficient vein graft material for conventional CABG (CO-CABG), have not been fully established. We therefore sought to compare the short- and long-term outcomes of patients >70 years old undergoing CO-CABG and TA-CABG. METHODS: We performed a retrospective observational study analyzing all consecutive adult patients aged >70 years undergoing first-time CABG over the 15-year period from 2004 to 2020 under a single surgeon. Primary outcomes of interest were in-hospital mortality, long-term mortality, and re-intervention rate. Secondary outcomes of interest included operative durations and the incidence of peri-operative complications. RESULTS: There were 46 patients (age 76 ± 3 SD) in the TA-CABG group and 145 patients (age 76 ± 4 SD) in the CO-CABG group. Cardio-pulmonary bypass and cross-clamp durations were comparable between groups (p = .11 and p = .23, respectively). Stroke occurred in 1.0% undergoing CO-CABG compared to 0% in the TA-CABG group (p = .42). Hospital mortality was 3.0% with CO-CABG (EuroSCORE; mean [SD] 6.81 (5.81)) and 2.0% with TA-CABG (EuroSCORE; mean [SD] 6.38 (6.57)) (p = .93). On long-term follow-up, myocardial infarction occurred in 10.0% of CO-CABG patients compared to 4.0% of TA-CABG patients (p = .25). Re-intervention rates were 7% following CO-CABG, and 2% after TA-CABG (p = .23). There was no significant difference in long-term mortality between patients undergoing CO-CABG and TA-CABG (47% vs. 57%, p = .27). Long-term survival was comparable between grafting techniques (p = .27). CONCLUSIONS: There were no significant differences in major adverse cardiac and cerebrovascular events, re-intervention rate, hospital or long-term mortality between CO-CABG and TA-CABG. TA-CABG represents a safe and feasible alternative to CO-CABG in elderly patients offering good long-term outcomes.


Subject(s)
Coronary Artery Disease , Myocardial Infarction , Stroke , Surgeons , Aged , Adult , Humans , Treatment Outcome , Coronary Artery Bypass/methods , Myocardial Infarction/etiology , Stroke/etiology , Retrospective Studies , Coronary Artery Disease/surgery , Coronary Artery Disease/etiology
19.
J Cardiothorac Surg ; 17(1): 243, 2022 Sep 30.
Article in English | MEDLINE | ID: mdl-36180915

ABSTRACT

OBJECTIVE: To describe the long-term outcomes of mitral valve repair (MVr) versus mitral valve replacement (MVR) in patients with native valve infective endocarditis (IE) at a centre with high-repair rates. METHODS: We conducted a retrospective single-centre cohort study. From 2005 to 2021, 183 patients with active or healed native valve IE were included. The primary outcome was long-term mortality. Patient status was last confirmed 31 March 2021. Secondary outcomes were post-operative MR, MV reoperation, length of post-operative intensive care stay and total hospital stay. RESULTS: 85 patients (46.4%) underwent MVr and 98 (53.6%) underwent MVR. Follow-up was 98.9% complete. Mean follow-up time was 5.3 years with 17% of patients reaching a follow-up time of over 10 years. There were 47 deaths (25.7%) within the follow-up period. MVR patients were more likely to have higher logistic EuroSCORE, active IE and were less likely to have elective surgery. In multivariate Cox proportional hazards analysis, there was no significant difference in long-term mortality between MVr and MVR groups (hazard ratio 1.09, 95% confidence interval [0.59-2.00]). In Kaplan-Meier analysis, MVR patients had a higher all-cause mortality although there was no significant difference at the endpoint. Propensity score matching analysis showed a significantly higher mortality in the replacement group instead (p = 0.002), Subgroup analysis revealed there remained no significant difference in mortality even in patients with active IE (P-interaction = 0.859) or non-elective surgery (P-interaction = 0.122). MV reoperation (odds ratio 1.00 [0.24-4.12]), post-operative intensive care stay (p = 0.9650) and total hospital stay (p = 0.9144) were comparable. CONCLUSIONS: Our data demonstrates repair was at least non-inferior to replacement in IE, supporting more aggressive use of repair. There is no reason the general principle of why repair is superior to replacement should not hold in IE, with enough operator expertise. Other experienced units should be encouraged to increase repair rates as feasible in line with current guidelines.


Subject(s)
Endocarditis , Heart Valve Prosthesis Implantation , Mitral Valve Insufficiency , Cohort Studies , Endocarditis/surgery , Humans , Mitral Valve/surgery , Mitral Valve Insufficiency/surgery , Retrospective Studies , Treatment Outcome
20.
Eur Heart J ; 43(29): 2756-2766, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35511056

ABSTRACT

AIMS: To assess the characteristics, management, and survival of patients with multiple native valvular heart disease (VHD). METHODS AND RESULTS: Among the 5087 patients with ≥1 severe left-sided native VHD included in the EURObservational VHD II Survey (maximum 3-month recruitment period per centre between January and August 2017 with a 6-month follow-up), 3571 had a single left-sided VHD (Group A, 70.2%), 363 had one severe left-sided VHD with moderate VHD of the other ipsilateral valve (Group B, 7.1%), and 1153 patients (22.7%) had ≥2 severe native VHDs (left-sided and/or tricuspid regurgitation, Group C). Patients with multiple VHD (Groups B and C) were more often women, had greater congestive heart failure (CHF) and comorbidity, higher left atrial volumes and pulmonary pressures, and lower ejection fraction than Group A patients (all P ≤ 0.01). During the index hospitalization, 36.7% of Group A (n = 1312), 26.7% of Group B (n = 97), and 32.7% of Group C (n = 377) underwent valvular intervention (P < 0.001). Six-month survival was better for Group A than for Group B or C (both P < 0.001), even after adjustment for age, sex, body mass index, and Charlson index [hazard ratio (HR) 95% confidence interval (CI) 1.62 (1.10-2.38) vs. Group B and HR 95% CI 1.72 (1.32-2.25) vs. Group C]. Groups B and C had more CHF at 6 months than Group A (both P < 0.001). Factors associated with mortality in Group C were age, CHF, and comorbidity (all P < 0.010). CONCLUSION: Multiple VHD is common, encountered in nearly 30% of patients with left-sided native VHD, and associated with greater cardiac damage and leads to higher mortality and more heart failure at 6 months than single VHD, yet with lower rates of surgery.


Subject(s)
Heart Failure , Heart Valve Diseases , Female , Heart Failure/complications , Heart Failure/epidemiology , Heart Failure/therapy , Heart Valve Diseases/surgery , Hospitalization , Humans
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