Search

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-1β), 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.

Background: Acute kidney injury (AKI) is a frequent complication of transcatheter aortic valve implantation (TAVI) and has been linked to preexisting comorbidities, peri-procedural hypotension, and systemic inflammation. The extent of systemic inflammation after TAVI is not fully understood. Our aim was to characterize the inflammatory response after TAVI and evaluate its contribution to the mechanism of post-procedural AKI. Methods: One hundred and five consecutive patients undergoing TAVI at our institution were included. We analyzed the peri-procedural inflammatory and oxidative stress responses by measuring a range of biomarkers (including C-reactive protein [hsCRP], cytokine levels, and myeloperoxidase [MPO]), before TAVI and 6, 24, and 48 hours post-procedure. We correlated this with changes in renal function and patient and procedural characteristics. Results: We observed a significant increase in plasma levels of pro-inflammatory cytokines (hsCRP, interleukin 6, tumor necrosis factor alpha receptors) and markers of oxidative stress (MPO) after TAVI. The inflammatory response was significantly greater after trans-apical (TA) TAVI compared to trans-femoral (TF). This was associated with a higher incidence of AKI in the TA cohort compared to TF (44% vs. 8%, respectively, p < 0.0001). The incidence of AKI was significantly lower when N-acetylcysteine (NAC) was given peri-procedurally (12% vs. 38%, p < 0.005). In multivariate analysis, only the TA approach and no use of NAC before the procedure were independent predictors of AKI. Conclusions: TAVI creates a significant post-procedural inflammatory response, more so with the TA approach. Mechanisms of AKI after TAVI are complex. Inflammatory response, hypoperfusion, and oxidative stress may all play a part and are potential therapeutic targets to reduce/prevent AKI.

Background: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG. Methods: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve–guided PCI. Quality of life was measured using the European Quality of Life–5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status. Results: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, –0.016 to 0.017]; P =0.946). The trajectory of EQ-5D during the 12 months differed ( P Conclusions: In the FAME 3 trial, quality of life after fractional flow reserve–guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02100722.

Anomalous origins of the right coronary artery (RCA) can cause ischaemia and sudden cardiac death, particularly if the RCA runs between the aorta and pulmonary artery. Conventional coronary artery bypass grafting (CABG) can be affected by early graft failure due to collateral blood flow. We present our institutional experience in managing patients with RCA anomalies.A single-center retrospective review of all patients who underwent surgery for aberrant right coronary arteries between 2005 and 2021 was conducted and in-hospital and long-term outcomes were analysed at our institution.A total of 10 patients (5 females, median age: 51 years, 36-62) were identified. They presented with symptoms of chest pain (n = 8), dyspnoea (n = 1) or following cardiac arrest (n = 1). In the majority the RCA originated from the left coronary sinus (n = 9). In one of those patients and one in whom the RCA originated directly from the left anterior descending artery CABG was performed. The other 8 patients were treated using transfer of the RCA ostium. All patients were discharged home (median hospital stay 5 days, range: 4-10). Four patients experienced post-op atrial fibrillation. No other complications were observed. At a median follow-up of 10 years and 9 months, 9 patients were alive and free from cardiac symptoms. One patient died 3 years postsurgery due to liver failure, unrelated to cardiac disease.In patients with an aberrant RCA, transfer of the ostium into the RCS carries a low surgical risk. It overcomes early graft failure in these patients, who present with a dynamic impairment in RCA blood flow. However, if fixed proximal RCA flow-limiting pathology exists, conventional bypass surgery is feasible.

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).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).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.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).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.

Human hearing loss is often accompanied by comorbidities like tinnitus. This perception of phantom sounds without external stimulation is affecting up to 15% of the adult population and can lead to psychological disorders like depression. Animal studies in rodents could show that tinnitus may not only be a result of hearing loss due to cochlear hair cell damage but can also be a consequence of synaptopathy at the inner hair cells already induced by moderate sound traumata (hidden hearing loss). In this study we investigate the synaptopathy previously shown in mice in our animal model, the Mongolian gerbil, and relate it to behavioral signs of tinnitus in this species. Tinnitus was induced by a mild monaural acoustic trauma leading to a monaural noise induced hearing loss in the animals quantified by auditory brainstem response audiometry. Behavioral signs of tinnitus percepts were detected by measurement of pre-pulse inhibition of the acoustic startle response in a gap-noise paradigm in about two-thirds of the animals. 14 days after trauma the cochleae of traumatized and non-traumatized ears were isolated and inner hair cell synapses were counted within several spectral regions of the cochlea. In the here presented preliminary data inner hair cell synaptopathy was only found in animals with behavioral signs of tinnitus, independent of type of hearing loss. On the other hand, animals with apparent hearing loss but without behavioral signs of tinnitus showed a reduction in amplitudes of auditory brainstem response waves I/II (cochlear nerve and dorsal cochlear nucleus) but no significant changes in the number of synapses at the inner hair cells. We conclude – in line with the literature – that hearing loss is caused by damage to the inner and / or outer hair cells but that the development of tinnitus, at least in our animal model is closely linked to synaptopathy at the inner hair cells.

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 patients70 years old undergoing CO-CABG and TA-CABG.We performed a retrospective observational study analyzing all consecutive adult patients aged70 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.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).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.

OBJECTIVES Since the turn of the century, cardiac surgery has evolved quite notably. This study sought to investigate the trends in aortic valve surgery activity and subsequent outcomes in the UK by using a mandatory national cardiac surgical clinical database within the context of a comprehensive public healthcare system (National Health Service). METHODS The UK National Adult Cardiac Surgery Audit database provided data for aortic valve surgery procedures performed between 2002 and 2016, and the data were validated and cleaned using reproducible algorithms. The findings and trends in in activity and outcomes were then analysed by financial year. RESULTS During the study period, a total of 148 862 procedures were performed, with the number of cases per year peaking in 2014/2015 at 12 483. The mean in-hospital mortality rate for all aortic valve surgery has fallen from 5.6% to 3.4%, despite an increase in patient age and mean logistic EuroSCORE. While the number of isolated aortic valve replacements has remained stable at around 5000 per year, aortic valve replacement and coronary artery bypass graft have increased to over 3200 with transcatheter aortic valve implantation activity continuing to increase. CONCLUSIONS This study demonstrates that despite an increase in patient risk profile, there has been a consistent reduction in in-hospital mortality within all aortic valve surgery procedures performed in the UK over a 15-year period. Increasing catheter-based interventions have not yet resulted in a significant decrease in surgical aortic valve replacements in the UK.

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.

OBJECTIVES Acute aortic dissection type-A (AADA) is a life threatening condition which requires emergency surgery. Surgery is usually performed by cardiac surgeons with various levels of aortic surgical experience. We compared the short-term perioperative outcome and long-term survival of patients operated by specialist aortic surgeons (SASs)and those who were operated by surgeons without specialist expertise. METHODS A single center retrospective review of 232 patients who underwent acute surgery for AADA was conducted between 2005 and 2020. The cohort was divided into those operated on by SASs (Group A, n = 186) and those operated on by nonaortic surgeons (Group B, n = 46). Statistical comparison was done using regression modelling and groups were propensity matched. Kaplan-Meier comparison was undertaken using STATA14. RESULTS Of 232 patients, 186 were operated on by an aortic specialist and 46 were operated by a nonaortic specialist. Overall 30-day mortality was 10% in Group A compared to 26.0% in Group B (unadjusted: p = .01, multivariate: p = .02, and propensity matched p = .05). Long-term mortality at 14 years was 26% in Group A compared to 52.0% in Group B (unadjusted: p = .001, multivariate: p = .001, and propensity matched: p = .01). Aortic surgeons performed a significantly higher number of aortic root procedures (43.0% vs. 17.3%, p = .001). The cross-clamp time and bypass time was significantly shorter in Group A patients (89 vs. 105 min, p

Objectives To investigate 4-year, post-transcatheter aortic valve implantation (TAVI) survival and predictors of survival by sex, in a real-world cohort that underwent transfemoral TAVI with SAPIEN 3 transcatheter heart valve. Background Previous TAVI investigations of first-generation devices demonstrated an early- to mid-term survival advantage in women compared with men. Methods SOURCE 3 (SAPIEN 3 Aortic Bioprosthesis European Outcome) is a post-approval, multicentre, observational registry. Patients (N = 1,694, 49.2% women, age 81.7 ± 6.7 years) with severe aortic stenosis and high surgical risk (logistic EuroSCORE 17.8%) underwent TAVI between 2014 and 2015. Kaplan-Meier event estimates were used to determine mortality by sex. Predictors of overall mortality were identified using a cox multivariate proportional hazard model. Results At 4 years, women had lower all-cause mortality than men (36.0 vs 39.7%; p = .0911; HR: 0.87 [95% CI: 0.75-1.02]). No difference was observed for cardiac mortality between women 24.2% and men 24.7% (p = .76; HR: 0.97 [95% CI: 0.79-1.19]). When adjusted for baseline characteristics (age, height, weight, NYHA functional class, renal insufficiency, EuroScore, and tricuspid regurgitation), sex had no impact on mortality. Conclusions In this large, real-world cohort, all-cause mortality trended lower in women than men at 4 years post TAVI; however, several baseline factors, but not sex, were predictors of mortality. No difference between sexes was observed for cardiovascular mortality.

A significant proportion of patients infected with the novel coronavirus, now termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), require intensive care admission and subsequent mechanical ventilation. Pneumothorax, a potential fatal complication of mechanical ventilation, can further complicate the management of COVID-19 patients, whilst chest drain insertion may increase the risk of transmission of attending staff. We present a case series and a suggested best-practice protocol for how to manage and treat pneumothoraces in COVID-19 patients in an intensive care unit setting.

Introduction Perioperative mortality of patients who undergo heart valve surgery for carcinoid heart valve disease has been observed to be high (5%-10%). We investigated whether peptide receptor radiotherapy with lutetium-177 dotatate can be used safely in patients with neuroendocrine neoplasm carcinoid heart valve disease and if there is associated survival advantage by reducing overall exposure of the valves to high doses of vasoactive peptides. Method Retrospective case notes review was performed on 18 neuroendocrine neoplasm patients (mean 60 years), who underwent heart valve surgery between 2003 and 2017 for carcinoid heart valve disease, 9 of whom received peptide receptor radiotherapy in addition to surgery. Results All patients were treated with somatostatin receptor antagonists and underwent cardiac valvular surgery (mean two valves replaced) and three benefitted from additional coronary bypass grafting. Nine patients underwent surgery alone: in this group, the time from surgery to progression was 14 months (mean; SD 13.5 months). Nine were treated with peptide receptor radiotherapy in addition to surgery. Six underwent surgery with peptide receptor radiotherapy on progression. Time to progression from surgery to first peptide receptor radiotherapy was mean 25.1 months (SD 23.6 months). No patients developed peritreatment cardiac complications. There were no deaths within the 30-day postoperative period. Average time from surgery to last follow-up/death was 41 months (6-79) in the surgery + lutetium group and in the surgery only group 17 months (1-24). Nine patients died, five in the surgery + lutetium group and four in the surgery only group, all at greater than 1-year postsurgery. Discussion Peptide receptor radiotherapy is safe in the setting of Carcinoid valvular heart disease in patients with controlled heart failure, PPRT can be use in the pre- and post-valve surgery period. There appears to be a survival benefit of having peptide receptor radiotherapy. Further evidence for peptide receptor radiotherapy in the neoadjuvant setting prior to cardiothoracic surgery is required.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed.RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group.CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Introduction: In mitral valve replacement (MVR), sudden increase in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes LV dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favourable 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 analysed a cohort of 29 MVR-P and 19 MVR-C patients with complete echo data at our unit, who were operated between 2012-2017. 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 - -15.5). There were no significant differences between all baseline demographics including age (p=0.45), underlying MV pathology (p=0.1), baseline LVEF (p=0.48) and GLS (p=0.15). There was significantly less worsening of GLS in MVR-C group as compared to the MVR-P group (p=0.023), indicating better preservation of LV function. There was also a lower decrease in LVEF in the MVR-C as compared to the MVR-P group, although the difference was not statistically significant (p=0.23). Conclusion: MVR with complete preservation of the sub-valvular apparatus shows a favourable 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.

Introduction: Minimally invasive cardiac surgery (MICS) has been gaining popularity over conventional sternotomy due to reduced invasiveness. However, in redo cardiac surgery when the risks are higher due to adhesions, few studies compare long-term outcomes. Objective: We aim to compare the perioperative and long-term mortality and stroke/TIA rate in patients undergoing median sternotomy and right thoracotomy for redo cardiac surgery. Secondary outcomes were post-operative and total hospital stay, blood products used, return to theatre and new renal replacement therapy (RRT). Methods: We retrospectively analysed a cohort of 127 sternotomy patients and 29 right thoracotomy patients for redo cardiac surgery between 2010-2020. All patients underwent valve repair or replacement. Patients requiring concomitant cardiac procedures were included. Results: In-hospital and long-term follow-up were 100% and 98.1% complete and a maximum of 10.4 years. There were 52 deaths (33.3%) within the follow-up period. Perioperative mortality was 16.5% in sternotomy versus 3.45% in MICS, although this difference was insignificant after adjustment for logistic EuroSCORE (HR 0.38, [0.05-2.79]). In multivariate analysis, long-term mortality was significantly lower in MICS (HR 0.30 [0.10-0.85]). Adjusted Kaplan-Meier curves revealed lower long-term mortality in the MICS group (p Conclusion: MICS for redo cardiac surgery is a safe and effective alternative to median sternotomy without compromising both short-term and long-term clinical outcomes.

Genetic variation in the transmembrane channel-like (TMC)6/TMC8 region has been linked to β-type human papillomavirus (HPV) infection and squamous cell carcinoma (SCC) of the skin and the head and neck, α-type HPV persistence and progression to cervical cancer. The functional variant rs7208422 of the TMC8 gene was suggested to have a high impact on susceptibility to β-papillomaviruses and their oncogenic potential and to also have an influence on α-type HPV-related disease. The aim of the present study was to evaluate a possible influence of rs7208422 on penile cancer risk, a known α-type HPV-related malignancy. Therefore, the distribution of rs7208422 was determined by direct Sanger sequencing of 104 Caucasian penile SCC cases and compared to data of 3,810 controls taken from the literature. HPV detection was performed by usage of GP5+/6+ primers and subtype-specific PCR. It was observed that the distribution of rs7208422 followed the Hardy-Weinberg equilibrium in both cases and controls. HPV DNA was detected in 39% of the penile SCC cases. Overall, there was no significant difference in the distribution of rs7208422 neither between cases and controls (P=0.726) nor between HPV-positive and -negative penile SCC cases (P=0.747). There was also no association between rs7208422 genotypes and age of disease onset (P=0.740). In conclusion, the present data argue against a significant impact of rs7208422 on the risk for the development of penile SCC in Caucasians. Even in combination with the HPV status, the SNP appears not to influence the risk of penile SCC in HPV-positive cases.

SUMMARY 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.

Glutamate is the major excitatory neurotransmitter in the CNS binding to a variety of glutamate receptors. Metabotropic glutamate receptors (mGluR1 to mGluR8) can act excitatory or inhibitory, depending on associated signal cascades. Expression and localization of inhibitory acting mGluRs at inner hair cells (IHCs) in the cochlea are largely unknown. Here, we analyzed expression of mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluR8 and investigated their localization with respect to the presynaptic ribbon of IHC synapses. We detected transcripts for mGluR2, mGluR3, and mGluR4 as well as for mGluR7a, mGluR7b, mGluR8a, and mGluR8b splice variants. Using receptor-specific antibodies in cochlear wholemounts, we found expression of mGluR2, mGluR4, and mGluR8b close to presynaptic ribbons. Super resolution and confocal microscopy in combination with 3-dimensional reconstructions indicated a postsynaptic localization of mGluR2 that overlaps with postsynaptic density protein 95 on dendrites of afferent type I spiral ganglion neurons. In contrast, mGluR4 and mGluR8b were expressed at the presynapse close to IHC ribbons. In summary, we localized in detail 3 mGluR types at IHC ribbon synapses, providing a fundament for new therapeutical strategies that could protect the cochlea against noxious stimuli and excitotoxicity.-Klotz, L., Wendler, O., Frischknecht, R., Shigemoto, R., Schulze, H., Enz, R. Localization of group II and III metabotropic glutamate receptors at pre- and postsynaptic sites of inner hair cell ribbon synapses.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is treated using oral/topical steroids and surgery. Despite maximal medical therapy, some patients remain recalcitrant. Mucus cystatin 2, pappalysin-A, and periostin can predict the presence of CRSwNP and correlate with disease severity. This study was designed to determine whether prospective sampling of these mucus proteins could predict medical failure and the need for revision surgery. Methods This investigation was an institutional review board‒approved, prospective study of 66 patients with CRSwNP. All patients underwent surgery, administration of topical/oral steroids, and outpatient mucus sampling at 10 time-points over 2 years. Five proteins, including cystatin 2 (CST2), pappalysin-A (PAPP-A), and periostin (PST), were analyzed and correlated with subjective parameters (including scores on the 22-item Sino-Nasal Outcomes Test [SNOT-22]). Variables were then analyzed and compared between those requiring revision surgery within 2 years (n = 5) and those with stable disease (n = 61). Results All patients demonstrated a significant decline in CST2, PAPP-A, and periostin after their initial surgery. The recalcitrant group demonstrated escalations in all proteins despite steroids, with levels higher than those of the stable group at 1 year (CST2: 258.1 ± 205.2 pg/mL vs 235.3 ± 275.7 pg/mL, p = 0.86; PAPP-A: 170.3 ± 150.4 pg/mL vs 74.6 ± 106.7 pg/mL, p < 0.05; periostin: 188.8 ± 192.4 ng/mL vs 54.5 ± 47.6 ng/mL, p < 0.001). Escalation in all proteins correlated significantly with worsening SNOT-22 score at each time-point (domain 1: 8.2 ± 1.3 vs 5.5 ± 1.1; p < 0.05). Conclusion Early recurrences and medical recalcitrance in CRSwNP may be predicted noninvasively through the serial, prospective sampling of mucus CST2, PAPP-A, and periostin levels. These biosignatures may help to predict disease course and guide individualized therapy.

Aortic paravalvular leakage (PVL) is a recognised complication of surgically replaced valves which is often treated using vascular plugs. Whilst transcatheter valve-in-valve therapy has been increasingly used for failed surgical bioprostheses, it is not considered as a treatment option for aortic PVL. However, the newer design of transcatheter aortic valves has a fabric skirt to create a more effective seal around the annulus. To our best knowledge, for the first time, we report successful adoption of the valve-in-valve therapy for the treatment of PVL in surgical bioprosthetic aortic valves such that the fabric skirt is placed immediately below the regurgitant orifice resulting in significant reduction in the PVL.

ObjectivesCongestion is associated with worse outcomes in critically ill surgical patients but can be difficult to quantify noninvasively. We hypothesised that plasma volume status (PVS), estimated preoperatively using a validated formula that enumerates percentage change from ideal plasma volume (PV), would provide incremental prognostic utility after coronary artery bypass graft (CABG) surgery.MethodsIn this retrospective cohort study, patients who underwent CABG surgery (1999–2010) were identified from a prospectively collected database. Actual ([1-haematocrit] x [a+(b x weight [kg])]) and ideal (c x weight [kg]) PV were obtained from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual−ideal)/ideal]).ResultsIn 1887 patients (mean age 67±10 years; 79% male; median European System for Cardiac Operative Risk Evaluation [EuroSCORE] 4), mean PVS was −8.2±9%. While 8% of subjects had clinical evidence of congestion, a relatively increased PV (PVS >0%) was estimated in 17% and correlated with lower serum sodium, higher EuroSCORE and a diagnosis of diabetes mellitus. A PVS≥5.6% was optimally prognostic and associated with greater mortality (HR: 2.31, p=0.009), independently of, and incremental to, EuroSCORE, New York Heart Association class and serum sodium. A PVS≥5.6% also independently predicted longer intensive care (β: 0.65, p=0.007) and hospital (β: 2.01, p=0.006) stays, and greater postoperative renal (OR: 1.61, p=0.008) and arrhythmic (OR: 1.29, p=0.03) complications.ConclusionsHigher PVS values, calculated simply from weight and haematocrit, are associated with worse inpatient outcomes after CABG. PVS could help refine risk stratification and further investigations are warranted to evaluate the potential clinical utility of PVS-guided management in patients undergoing CABG.

Mucus consistency affects voice physiology and is connected to voice disorders. Nevertheless, the rheological characteristics of human laryngeal mucus from the vocal folds remain unknown. Knowledge about mucus viscoelasticity enables fabrication of artificial mucus with natural properties, more realistic ex-vivo experiments and promotes a better understanding and improved treatment of dysphonia with regard to mucus consistency. We studied human laryngeal mucus samples from the vocal folds with two complementary approaches: 19 samples were successfully applied to particle tracking microrheology (PTM) and five additional samples to oscillatory shear rheology (OSR). Mucus was collected by experienced laryngologists from patients together with demographic data. The analysis of the viscoelasticity revealed diversity among the investigated mucus samples according to their rigidity (absolute G’ and G”). Moreover some samples revealed throughout solid-like character (G’ &gt, G”), whereas some underwent a change from solid-like to liquid-like (G’ &lt, G”). This led to a subdivision into three groups. We assume that the reason for the differences is a variation in the hydration level of the mucus, which affects the mucin concentration and network formation factors of the mucin mesh. The demographic data could not be correlated to the differences, except for the smoking behavior. Mucus of predominant liquid-like character was associated with current smokers.

Background: ST2 is a circulating biomarker that is well established for predicting outcome in heart failure (HF). This is the first study to look at ST2 concentrations in optimally treated patients with stable but significant left ventricular systolic dysfunction (LVSD) compared to patients with severe aortic stenosis (AS). Methods: Two cohorts were retrospectively studied: 94 patients undergoing transcatheter aortic valve implantation for severe AS (63 with normal ejection fraction [EF] and 31 with reduced EF), and 50 patients with severe LVSD from non-valvular causes. ST2 pre-procedural samples were taken, and repeated again at 3 and 6 months. Patients were followed-up for 2 years. Data was analyzed using SPSS software. Results: Baseline concentrations of soluble ST2 did not differ significantly between the HF group and AS group with normal EF (EF ≥ 50%). However, in the AS group with a low EF (EF < 50%) ST2 concentrations were significantly higher that the HF group (p = 0.009). New York Heart Association class IV HF, baseline N-terminal pro-B-type natriuretic peptide and gender were all independent predictors of soluble ST2 (sST2) baseline concentrations. Conclusions: Raised ST2 concentrations in the context of severe AS may be a marker for subclinical or clinical left ventricular dysfunction. More research is required to assess its use for assessment of prognosis and response to treatment.

ObjectivesCongestion can worsen outcomes after transcatheter aortic valve implantation (TAVI), but can be difficult to quantify non-invasively. We hypothesised that preprocedural plasma volume status (PVS), estimated using a validated formula that enumerates percentage change from ideal PV, would provide prognostic utility post-TAVI.MethodsThis retrospective cohort study identified patients who underwent TAVI (2007–2017) from a prospectively collected database. Actual ([1-haematocrit] × [a + (b × weight (Kg))] and ideal (c × weight (Kg)) PV were quantified from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual – ideal PV)/ideal PV]).ResultsIn 564 patients (mean age 82±7 years, 49% male), mean PVS was −2.7±10.2%, with PV expansion (PVS >0%) evident in 39%. Only logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) independently predicted a PVS >0% (OR 1.85, p=0.002). On Cox analyses, a PVS >0% was associated with greater mortality at 3 (HR 2.29, 95% CI 1.11 to 4.74, p=0.03) and 12 months (HR 2.00, 95% CI 1.23 to 3.26, p=0.006) after TAVI, independently of, and incremental to, the EuroSCORE and New York Heart Association class. A PVS >0% was also independently associated with more days in intensive care (coefficient: 0.41, 95% CI 0.04 to 0.78, p=0.03) and in hospital (coefficient: 1.95, 95% CI 0.48 to 3.41, p=0.009).ConclusionHigher PVS values, calculated simply from weight and haematocrit, are associated with greater mortality and longer hospitalisation post-TAVI. PVS could help refine risk stratification and further investigations into the utility of PVS-guided management in TAVI patients is warranted.